NOTE: This spoiler was submitted by Spectre.
We open in a vampire hive, Mira Soral. We see a group of warriors led by a man simply named Priest (Paul Bettany). He walks with them into the cavern and stops. He listens closely and senses something. "It's a trap." he says. Suddenly, vampires burst out of every pocket of the hive. One burrows from underground and grabs a warrior and kills her. Rapid cuts show the warrior priest's panicking and trying to escape while several are kille. At the exit of the hive, one of the priests is being dragged away by the vampires. Priest tries to save him but he loses his grip. He screams in anguish.
An animated sequence explains that since the beginning of time vampires and humans have been fighting each other. Vampires have speed and superior strength. However, they were weakened by the sun which the human took advantage of. However, the war quickly reached a stalemate. The Church, wanting to end it, commissioned a sect of warriors called Priests, trained to kill vampires. They quickly cut a swath through the vampire army and those who were left were sent to guarded reservations. The Church, fearful of the weapons they trained, effectively betray them by disbanding their sect and making them rejoin society. Problem is, no one trusts them.
We cut to a house in the middle of nowhere. A farmer, Owen Pace (Stephen Moyer) looks at a reading of the soil. He goes to his wife Shannon and tells her that possibly they will be able to plant crops soon. Their daughter Lucy Pace (Lily Collins) comes home soon after saying she was in town. Owen tells her he doesn't like her going out often as it is not safe. Lucy says she doesn't want to be a prisoner here just so he MIGHT be able to grow food. Shannon shushes them both and they begin to say grace for dinner when Owen hears something. He looks out and sees something. Vampires. He orders Shannon to get Lucy underground and grabs a stake gun. Lucy goes into a bunker under the table and Shannon tells her daughter not to scream no matter what happens. The vampires break in and begin to attack. Owen gets in a few shots before they are overrun. Lucy watches in horror her mother be killed. Her body hits the floor and is dragged away. Despite staying quiet, someone finds the bunker. A shadow looms over her and she screams.
We cut back to a city where the human race has allowed itself to be sealed in, their every decision made for them by The Church. They are constantly reminded "That an act against the Church is an act against God." Priest is walking home from his menial job as a coal shoveler. He goes to confession, which is more than an automation. He sighs at the canned advice he is given in regards to his problems (his nightmares in regards to the hive incident). He goes home.
There, he senses something and puts a knife to a man's throat. The man is Hicks (Cam Gigandet), the sheriff of an outskirts town. He's here to tell him that Lucy has been kidnapped, Owen (Priest's brother) is gravely wounded and Shannon was killed. Hicks is going after her and wanted to see if Priest wanted to join him. Hicks leaves.
Priest goes to the council of high priests and asks to be reinstated to his duties to go save his niece since it was a vampire attack. The council lead by Orleas (Christopher Plummer) denies his request saying vampires had been eradicated and they will not allow it. Chamberlain (Alan Dale) who is more sympathetic tries to get the council to change its mind as Priest has them served well but Orleas overrules him. Orleas tells Priest if he tries to leave to save Lucy, it will be considered a slight against The Church and thus God. He will be stripped of his rank and be excommunicated.
Priest goes to a bar with Chamberlain and muses that he gave up everything for The Church and they abandon him when he needed them most. Chamberlain reminds him he cannot break his vow. Priest says they left him with no choice. Chamberlain motions for armed guards and Priest realizes what his answer is. He fights the three guards and kills them. He gets on to his motorcycle and leaves to the outskirts away from the city until he gets to his brother's house. He sees it in disarray and pockets a family photo. Hicks comes in thinking he is a burglar, but realizes it is Priest. They race off to town.
In town, a Salesman (Brad Dourif) is trying to con the people for vampire protection. Hicks breaks that up quickly, running the Salesman out of town. He tells the people that they don't need to be scared of vampires. The people look at Priest warily. They don't get many visitors out here.
Priest can see his brother. Owen says he is sorry he couldn't save Shannon. She never forgot Priest (It's inferred they were in a relationship before his calling). Priest said Owen gave her a life that he could no longer could. Owen tells Priest to get Lucy and promise to "kill them all."
Priest and Hicks talk. Priest wants to go alone, but Hicks proves he is no rookie by slicing a bullet with a knife throw. Priest says they leave at dawn. He continues to carve crosses into bullets for Hick's guns.
Lucy wakes up in a cage on a moving train. A vampire is looking at her hungrily but he is thrown back by his boss Black Hat (Karl Urban). Lucy tells him that her uncle is a Priest, and he will come after her and kill him. Black Hat says he is counting on it.
In the morning, Owen succumbs to his wounds and is buried with Shannon. Priest looks on in sadness. Priest and Hicks go back to their house and find tracks that go north towards a vampire reservation. They ride towards that.
Back in the metropolis, four former Priests are called by the The Church, including Priestess (Maggie Q) who fought with Priest. Orelas tells them Priest has broken his vow and he is to be brought back to Orleas dead or alive.
Priest and Hicks arrive at the reservation and notice their are no guards there. A vampire sees Priest and says he is not welcome. They ask if anyone came through; the vampire says no. Priest and Hicks go down a bunker and encounter a cowering vampire. Priest asks where the girl is but he will not give up any info. Hicks is nearby and sees three other vampires approach him looking for a fight. It's a trap. One throws an Ax at Hicks but he dodges it, then throws it right back at the vampire, killing him. Getting back outside, Hicks and Priest kill the other two vampires. The vampire they originally talked two tells them (under duress that is) that Lucy was taken West on a train but it won't matter. They are only going to be alive for ten more seconds.
The sun sets and the sky turns dark and the more ferocious vampires come out to kill Priest. He pulls out a book and says some words. It is just a ploy to lull his enemies into false security as he is really setting off mechanized bladed crosses which kill the vampires. With nothing more to gain there, Hicks and Priest leave.
Priest realizes that west of the reservation is a former vampire hive. Mira Soral. The place where he lost several of his comrades. Hicks and Priest head towards it. Halfway there, Priest finds out Hicks was Lucy's boyfriend and he loves her. Priest tells him if Lucy is infected, he will kill her. Hicks says that will not happen; he already failed protecting her, he will not make the same mistake twice.
Black Hat has a meeting with The Salesman on the train. The Salesman tries to talk money with Black Hat before giving up his info but Black Hat just threatens him. The Salesman says Hicks and Priest came through town looking for Lucy. Black Hat said he has down well then drains him to the brink of death, making him his slave. "There's your compensation." Black Hat snarls.
Priest and Hicks enter the hive but find it abandoned. Priest goes off alone and is confronted by Priestess. Priestess says she is here to warn him; The Church sent her and three others to capture or kill him. She sent the others to Jericho city while she came here. She's not here to stop him, she wants to help him. They hear a gun shot. Hicks is in trouble.
Hicks sees a large beast that attempts to get at him. However, as Priest points out it is quite too large to get to him and that is the only reason he is still alive. Priest and Priestess work together and kill the vampire beast. Priest realizes that the vampires are rebuilding their army but he doesn't know how they can travel quickly.
Hicks talks to Priestess and learns some things. The Priest sects are required to take a vow of celibacy for life. Since she was a little girl when The Church recruited her, that means she has never had sex. Meanwhile, Priest was recruited when he was Hicks' age making it more difficult. "His sacrifice was greater." Priestess says (Priest had to leave Shannon).
Hicks, Priest, Priestess find a new tunnel that leads right out to Jericho city, where she sent the other three. They realize that is where the vampires our heading.
A conductor is asleep when he hears a train roar in unannounced. He looks around for anyone, and is quickly killed. The vampires break out and proceed to slaughter the entire town, while Black Hat watches in glee. Just then the three Priest warriors show up, ready to fight. Black Hat take his hat off, and shows he has a Priest tattoo (he was the one that Priest was unable to save during the hive incident). One Priest tries to kill him but Black Hat just punches him away. The Priest looks down and notices a great wound. Black Hat just didn't punch him; he tore out his heart. He falls to the ground dead. Black Hat tells the remaining two they can either join him or die. The Priests prepare to fight.
Priest, Hicks, and Priestess arrive in town too late to save anyone. All the bodies are gone and their is nothing but blood. Priestess looks around and finds some explosives and grabs them up. They find the train tracks and realize that is how the vampires are traveling. The tracks lead back to the cities where The Church has walled everyone up. Hicks says the sun would kill them, but Priest says their is no sun there anymore. It will be a massacre.
Priest and Priestess talk. She gives him a large cross of his that she kept from the old days. She tells him that he is doing the right thing. The Church didn't give them their powers; God did. She says he is a Priest no matter what they say and touches his face. Priest says he can't (Priestess is implied to be in love with him). Priestess is crushed and says that when she heard Shannon died she prayed for her then for herself because she selfishly thought with Shannon dead, Priest would be free to love another (like her). Despite all this, the three get on their bikes and head for the train, ready to stop the vampires.
Lucy is taken to dinner with Black Hat. He exposes on that vampires have been considered to have no soul but he has seen it and it is more pure than any human. He plans to evolve the species, by force if necessary. Lucy grabs a knife from the table, something that Black Hat does not notice.
About to board the train, Hicks confronts Priest and says he will not kill Lucy. Hicks asks why does Priest care about Lucy since he is a stranger to her. Priestess reveals that Priest is Lucy's father. She was just a baby when he was called by The Church. Hicks says that's not possible for he knew Owen well. Priest says "The child needed a father. We all make sacrifices."
They speed off in their cycles. Priestess is to sprint ahead and plant the charges to blow the tracks. She is to detonate even if they are still on the train.
Hicks gets on from the very back of the train and has to wade through cocoons filled with vampires.
Priestess is chased by a gang of motorcycle bandits. She uses nitro to evade them and begins to set the charges.
Priest jumps on top of the train where Black Hat is there waiting. Black Hat reveals him as his former comrade and says that night he fed upon until the Vampire Queen showed mercy and made him a human vampire. a "daywalker". Priest can either join him or die. Priest asks where his daughter is. "Awaiting your answer." Black Hat says. Priest and Black Hat fight and despite Priest's excellent training he is no match. Black Hat punches him off the train. But Priest is able to hang on underneath.
Hicks catches up to Lucy but a vampire runs off with her. Priest breaks through the floor and joins him to get her back.
Meanwhile, the bikers have caught up to Priestess. She uses a long sharp chain to hook on to their bikes and flip them into each other, killing them. The last man who charges her, she flips him off his bike, then dismembers him mid air, pieces of him falling all around her. However, in the fracas, the bomb was damage beyond repair. Not knowing what to do, she looks at the explosives then her bike. She forms a plan.
Hicks and Priest find Black Hat, Lucy, and the Vampire guard in the main compartment. Hicks tries to kill Black Hat but he is literally knocked out of the train. Lucy grabs a lantern and burns the vampire holding her. She goes to stab Black Hat but he stops the blade between his hands. "Quick, yes, just like your father." Black Hat says, looking at her. Lucy looks at Priest and realizes he is her father. "Oh you didn't know?" Black Hat says. He pins Priest to a wall with a blade then takes Lucy back up to the roof of the car.
Hicks gets up and sees a fallen vampire's bike. He gets on it to catch up with the train.
Priest pulls out the large cross Priestess gave him and pulls out the knife pinning him. He gets back up to the roof just as Black Hat is about to bite Lucy. The Cross actually hides a knife which Priest throws into his neck. Black Hat tries to throw Lucy off but Priest grabs her. Black Hat stomps on Priests hand trying to kill them both. However, they all see Priestess racing towards them with the explosives strapped to her bike. Priest and Lucy jump off just before the two collide. The explosions makes the train jump off the rails and engulfs Black Hat in a sea of flame.
Priest holds Lucy, his daughter, just glad she is alive. Hicks finds them and he and Lucy embrace. Priest sees Priestess in the distance. She survived the bombing run.
Priest goes back to the metropolis and confronts Orelas with a vampire head, proving they are not eradicated. Priest says their is a train wreck full of them. Orelas calls him a charlton and continues to deny that vampires are still a force to be reckoned with. "The war is over!" Orleas screams. "No." Priest whispers to himself. "It has just begun."
Priest leaves the city again and meets up with Priestess, who has decided to stand by him in the conflict.. She has contacted the remaining Priest warriors and they will follow him as their commander. They are to meet up in City Seven. Priestess wishes him God Speed and Priest rides off, ready to face the new chapter in the vampire war.