The movie opens in a small town in Germany in 1796. Young Will Grimm is sitting in a dank little cottage with his mother and his sister Lotte, who is coughing and obviously ill. He assures his mother that Jacob will be home soon with money from selling the cow, and they can get Lotte a doctor. Moments later, Jacob bursts through the door holding a handful of beans--magic beans that can make Lotte better, he explains; he got them from a man on the street. Will is furious and throws the beans to the floor.
Fifteen years later, the brothers ride into French-occupied Karlstad, Germany. They are taken to the mayor and are told stories by the villagers about the witch of the mill. The townspeople are obviously frightened and say that they have no one else to turn to; Jacob records the details of their stories and Will prepares a bill, which he shows to the shocked mayor, who says "It better be worth it."
The brothers Grimm are preparing in the mill for the fight against the witch. They wear shiny armor which supposedly repels evil, and they have the miller hide with a shield (but still able to see all the action). The witch comes swooping in, and a fight ensues in which Will shouts that the brothers Grimm do not fear her, Jacob tries to shoot the witch with an arrow full of baby's tears--the only way to kill a witch--and misses, and the witch uses her power to control the brothers' swords so that they are at each other's throats, until they break free and shoot the witch. She becomes a pile of snakes on the floor, and the brothers cut them up and place them in a bag, advising the man to place them in a mirror-lined box and collecting their fee. Moments after the miller leaves the witch comes swooping back in, and we learn that it was all an elaborate theatrical hoax: the witch is an associate of theirs, and another man was pulling strings that made him fly, and there are springboards in the floor to make it appear as if they were shot back by magic.
Cut to the forest of Marbaden. A little girl in a red riding cape is picking flowers in the forest, humming to herself. She hears a growl and sees a movement in the trees. She walks a little faster, then breaks into a run, dropping her basket as she goes. As she runs across a field toward the village she trips, and screams as whatever was chasing her obviously catches up. A one-legged man with crutches steps outside to see what all the fuss is, and sees a red riding cape hanging in the trees.
That night the brothers are carousing in a tavern. Some French soldiers arrive and threaten to kill the mood--the French are wildly unpopular in Germany. Will saves the situation by offering them wine. Later, Will hooks up with two local girls and tries to convince Jacob to take one, but he is not interested. Will yells something at him about "magic beans." (This keeps coming up--Will won't let Jacob live it down.)
Later as they are sleeping in a room at the inn, an Italian man bursts in with a couple of French guards and points weapons at them. More guards set fire to the brothers' horses' tails, and the horses run wildly through the streets. Jacob looks down sleepily and notes that Will has rope around his ankle just before they are dragged off, then the rope is cut, Will tries to escape, and they are both caught and taken away.
The brothers are brought before General Delatombe, who appears to be in charge of the French forces in the area. He has coaxed confessions out of the brothers' two associates by hanging them upside down, with snail-filled glass boxes on their heads, and accuses them of theft and humbuggery, for which the penalty is death. Cavaldi, the Italian man, is desperate to drop the two associates into a vat of boiling oil, but Delatombe refuses, telling the brothers that if they can take care of a problem he is having with a haunted forest in the village of Marbaden, he may consider amnesty. Nine girls have gone missing from the village, and he believes that if the rumor of this haunting is spread, it could cause panic and problems for the French, yet he is sure that it is another group of tricksters like the brothers.
Cut again to the forest of Marbaden, where a brother and sister are walking through the forest looking for the missing girls. Their names are Hans and Greta, and they are dropping bread crumbs which a number of large black birds (ravens, I think) are eating. Greta approaches a stream to cross and her shawl blows off of her shoulders, floating down the stream. She goes after it, but it keeps blowing just ahead of her. She follows it down to a small cave, where it begins to get sucked into a hole in the wall. She grabs it and pulls it out, and we see a strange pattern of circles and an angry moon carved into the rock. As Greta pulls out the shawl, thousands of beetles come pouring out of the hole. She screams. We then see Hans looking for his sister. He can't find her anywhere, but sees a raven holding a piece of her shawl.
The brothers Grimm arrive in Marbaden. They are pulled from their prison cart and instructed by Cavaldi to go find people. The town appears deserted. Jacob approaches a window and has a gun pointed at him; various villagers come out with an assortment of weapons, and Will attempts to explain that they are the famous Brothers Grimm. No one has heard of them except one child. The townspeople take the brothers to their meetinghouse, where they explain the situation with the missing girls and the strange things in the forest. Jacob records all the details in his book. Will announces that they will need a guide through the forest, and it appears that the only person who can help them is the trapper Kraus, who is cursed.
It turns out the trapper, Kraus, is actually a woman named Angelika. Two of her sisters were taken by the forest. She refuses to help them but they force her to anyway. They tie up their horses and walk further in. Angelika leads them through the forest, to a huge tower in a clearing surrounded by several crypts. She tells them the story that her father used to tell them, about a vain queen who hid in the tower to escape the plague, forgetting that it carried on the wind. She fell ill, but having stolen the spells of the forest people, she cast a spell to give herself eternal life. Angelika tells them that the Christians cut it down, but it grew back. While she is telling the story, a mysterious figure approaches Jacob's horse and feeds it a lot of spiders. Back at the tower, Will says that it's time to go and begins to head off, but Angelika tells him it's the wrong way, not to trust the trees. She licks a toad and asks it which way to go, then leads them back to their horses. They ride back into town and Angelika tells them that tomorrow they're on their own; she prefers to do things her own way.
Cavaldi sets the Grimms to work scrubbing the floor and doing other chores, making them wear aprons and bonnets. That night as they are sleeping Jacob's horse begins acting strangely. A young girl named Elsie wakes up and hears the horse saying "help me." She walks into the stables and pets the horse, telling it what big eyes and ears it has, and such a pretty mouth. A spider crawls out of the horse's mouth and Elsie is horrified; suddenly a long rope of spiderweb shoots from the horse's mouth and traps her. She struggles against it, but it continues to wrap around her, forming a cocoon. The horse flings her into the air and swallows her whole. The brothers are awakened by the noise and run down to the stables to see the horse charging off, then Angelika riding after. Will tries to explain it logically but can't. They ride off after Angelika, followed by Cavaldi and his men.
In the forest, Angelika is torn from her horse by a moving tree. A large wolf emerges from a cave and stares her down. She believes this is the wolf that killed her father years before, but as she fights it she notices that it has her father's eyes. Meanwhile the brothers try to fight their way through the forest, but a couple associates are killed by the trees or the wolf.
Somehow the brothers hook up with Angelika and run out of the forest, where they are apprehended by Cavaldi, who ties them up and takes them back to Delatombe. Angelika is placed in a giant food processor-looking contraption, and Cavaldi begins lowering the blades toward her. Will shouts that they know who was behind it and that they can finish the job is they can go back and do things their way, and Delatombe agrees and has Cavaldi stop the blades just before they chop Angelika to bits.
Jacob is obviously beginning to believe in the enchantments of the forest, while Will is holding out. They both agree that they will need Angelika's help, so Jacob goes to talk to her. He is falling for her, and tries to convince her that it's real and she believes, and they need her. Will comes in and yells at him again about magic beans, and makes Jacob go wait by the cart. Will and Angelika begin to talk about how Jacob makes Will feel weak and how he can't protect him, and they are about to kiss when Jacob walks in wearing the armor from the beginning. He gets mad and runs off, mounting his horse and heading for the forest. Will starts to go after him, but Cavaldi pins Angelika against a wall and she tells him to go on.
Jacob is in the forest attempting to set up a catapult to enter the queen's tower. Will arrives just as they launch it, and Jacob's body slams against the tower and falls to the ground. It isn't anywhere near high enough. Will runs over, panicked, thinking him dead, then sees it is just a dummy. Jacob appears behind the catapult, perplexed, and Will begins to tell him off again. Jacob says that all he wants is for Will to believe in him, because for once this story is true, and Will agrees. He says that Jacob is overcomplicating it, and a grappling hook and rope would probably work better. The associates, however, are noticing the moving trees and run away.
Back in town, Angelika is tied to a chair and Cavaldi is acting smug. A little girl named Sasha goes out to get water, and a raven dive-bombs the well and splashes in. Sasha pulls it out of the well and holds it up, sad. Suddenly the raven begins flapping its wings and spraying black tar-like stuff on Sasha. A puddle of it forms on the ground, and two eyeballs pop up out of it. Sasha wipes the goo off of her face and we see that her face is gone. Angelika hits Cavaldi and runs out, calling to Sasha to follow her voice. The goo forms a tar-baby shape with Sasha's face and runs after her, but Angelika grabs her and tells Cavaldi to take her inside. Angelika manages to cut the tar baby in half but it slithers under the door and pulls Sasha out, where she collides with it and becomes a gingerbread man. Sasha laughs and jumps into the well.
Jacob is scaling the tower on the rope. He makes it to the top, where the rope snaps and he is stuck on the roof. He swings himself down and into the tower room, which is dusty and inhabited by ravens. There is a spellbook on a table, some candles, a crown, and a bed on which rests a disgusting old body with long hair and fingernails. He also finds a piece of parchment with the same pattern as was on the cave wall, recognizing the blood moon. Jacob sees a brilliant room through a doorway and tries to enter it, then realizes it to be a magic mirror that shows the same room in all its glory. The queen begins to speak to him, and in the mirror he sees her, beautiful, promising him anything he could ever want.
Meanwhile, on the ground, Will sees a young girl's body surface from the stream. He tries to get to her but hears someone else. The wolf approaches and transforms into a man dressed in heavy furs, who picks up the limp body and carries it to a crypt. He places glass slippers on her feet and beetles begin to close the crypt. Will, however, manages to pull the girl out and somehow get the wolf-man's axe in a fight that ensues. He licks a toad to find the way out of the forest, then throws a rock up into the tower window to get Jacob's attention and makes a crack in the mirror. Jacob suddenly realizes what is happening and slides down the tower holding a piece of the queen's hair as a rope. As they flee, the trees start to close, but by holding up the axe Jacob makes the trees back away and they escape.
The girl in the crypt was Sasha, and they take her back to town and try to revive her. Jacob explains that the queen is probably using the girls to regain her youth and beauty and it will happen at the blood moon. Sasha was meant to be the twelfth but now she needs another one. As they are warning the people, the French led by Delatombe ride into town and say that they will solve the problem by burning the forest and with it the Brothers Grimm. Cavaldi brings Angelika up, and she sees the axe, recognizing it as her father's. She tries to grab it. Delatombe ridicules Cavaldi for wearing the silver armor the brothers had made.
That night, the night of the blood moon (a total lunar eclipse), the French tie the brothers to ladders in the forest and light it, throwing Jacob's record book on the flames. Delatombe and Cavaldi watch the forest burn while sipping wine and dining. Angelika, who has somehow gotten the axe, slips through the forest under a wolf skin and cuts them free, but Jacob must leave his book behind. They run through the forest away from the flames, and Angelika sees her father as a wolf. He changes and they stare at each other. We learn that Angelika's father was hunting in the snow and collapsed from the cold. The ravens carried him to the tower, where the queen pulled her mirror trick and stabbed something into his heart to make him subservient to her. He has been doing her bidding ever since. Angelika tries to return her father's axe, but the brothers are smart enough to realize he will kill her and manage to get it back. They run to the tower, but Angelika is captured and placed in the twelfth crypt. Her father takes a drop of blood from her finger and closes her in, then the ravens carry him up to the tower.
As the queen awakens in her tower, a wind blows across the forest and puts out the fire. The Frenchmen are all astonished to see the brothers missing, and many soldiers run in fear. Delatombe shoots some men who are running, then takes Cavaldi and his valet into the forest to search for the brothers.
Angelika's father is being congratulated by the queen in her tower for getting the twelve girls. He seats her on the throne and places the old crown on her head. Meanwhile down below Will and Jacob are trying to figure out how to get up to the tower without a rope. They begin looking through their supplies when Delatombe, Cavaldi, and the valet arrive. Delatombe orders Cavaldi to kill them, but Cavaldi, who is beginning to believe in the story, says that he wishes to resign his position. Delatombe shoots him in the chest and he falls onto a crypt. Delatombe and the valet chase the brothers, and Will throws the axe at the valet, missing him. Just before the valet kills him, the axe boomerangs back and hits the valet in the back, killing him.
Jacob is working at the catapult, trying to get it to work, and Will and Delatombe make it up onto a rocky ledge where they fight. Will falls to the ground, and Delatombe tells him to beg. Jacob throws something up to Will--a golden cross--and Will begins an overly theatrical begging routine, before snatching up the cross (a prop that catches fire) and throwing it in Delatombe's face, grabbing his sword and stabbing him. As Delatombe falls he dislodges a chunk of rock, which falls onto the catapult and sends Jacob flying into the air and into the tower window.
Angelika's father is performing the spell to revive the queen, giving her the blood of the twelve girls in a cup. We see the twelve crypts opening, and the girls' feet clicking together in their glass slippers. Jacob grabs a knife and runs at them, but the queen raises her hand and pins him to the wall. Will, down below, sees a piece of the queen's hair hanging down. It is wrapped around Jacob's waist, and as Will climbs it, Jacob winces. Will arrives, axe in hand, and tries to attack the queen, but he too is pinned to the wall. The queen uses her powers to make them attack each other, and as they hang in the air, holding each other's weapons back, Will tells Jacob that he trusts him and that it is his, Jacob's story. He let's go of his brother's arm and Jacob stabs him. They fall to the ground, and in the mirror the beautiful queen begins speaking to Will. She offers him life, and he crawls over to her ancient body on the throne. The queen turns to Angelika's father and, despite his pleas, pulls the magic spike out of his heart and puts it into Will's. Angelika's father falls to the ground and Will is revived. The queen, who has been growing younger and more beautiful as the eclipse progresses, makes Will stand beside her, and asks him who is the fairest of them all. He replies that she is and leans in to kiss her; Jacob cries out at this, telling him not to, and smashes the magic mirror.
The queen begins to fall apart, shattering as the mirror does. The ravens fly away, and Angelika's father, now free from the witch's spell, rushes at her, wanting revenge for his daughters' deaths. Will leaps at him and they fall out of the tower window to the ground. Cavaldi, who was lying on the crypt, awakes and pulls back his cloak to reveal a bullet lodged in the brothers' silver armor. He runs over and drags Will's body to safety as the tower collapses.
Amid the rubble Cavaldi searches for Jacob, whom he finds under the queen's mattress. He takes him to where Will is lying, not breathing. Even after he removes the queen's spike, Will is still. Jacob feels he has let his brother down. Cavaldi says he remembers this story from his childhood, and it isn't too late to break the spell. The two of them go to Angelika's crypt, and Cavaldi says that a kiss of true love can break the spell--but it must be true love, or it will be the kiss of death. Jacob leans in and kisses Angelika, who doesn't move. After several tense moments she gasps and awakes. All of the girls are getting up and running to hug each other. Jacob runs over to where Will is lying and tells him to wake up. He drops down beside his body, stunned. Cavaldi says, "Perhaps another kiss?" and as Jacob leans down, Will mutters, "Not you." Jacob tells Angelika to give it a try, and as she kisses him, Will embraces her and says "I just had to know what that was like before the story was over."
The entire group returns to the village to a hero's welcome. There is a big party with dancing and feasting and Cavaldi is proud to be part of the group. Angeliks tells the brothers that they are welcome back anytime. Cavaldi hands Jacob his book and tells him he should be more careful with it. As they walk towards the festivities, Will tells Jacob that he has another idea to make money, and Jacob points out that they have nothing to their name--but they agree that it is a fine name.
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