NOTE: This spoiler was submitted by Jeremy

The film starts in the 90’s where a Great Dane puppy (Frank Welker) steals a rack of gyros from a shop. He is chased by a police officer and ends up coming across a lonely little boy, Norville “Shaggy” Rogers (Iain Armitage). Shaggy shares his sandwich with the puppy, who adds some of the gyro meat to it. The officer finds the dog and asks Shaggy if it’s his and what his name is. He names the dog Scooby Dooby Doo, and the officer leaves. Shaggy brings Scooby home where he gifts him his trademark collar. From then on, the two become the best of friends.

On Halloween night, Shaggy and Scooby dress up as their heroes, the Blue Falcon and Dynomutt. They pass a spooky house and get harassed by bullies who throw their candy into the house. Moments later, they meet a trio of friends, Fred Jones (Pierce Gagnon), Daphne Blake (McKenna Grace) and Velma Dinkley (Arianna Greenblatt). They decide to go inside the house together, where they come across what appears to be a ghost. The kids are trapped in the house until Fred and Velma spot the string holding the ghost up, and they cut him loose. They unmask him as local man Mr. Rigby (Tony Cervone), who is also stashing stolen store products. He is arrested and blames his misfortune on those meddling kids. The four friends and Scooby all then vow to continue solving mysteries together as Mystery Inc.

After a recreation of the original show’s intro, we catch up with the gang as adults in a restaurant. Fred (now played by Zac Efron), Daphne (now played by Amanda Seyfried), and Velma (now played by Gina Rodriguez) want to take Mystery Inc to new heights as a serious company. Scooby and Shaggy (now played by Will Forte) are content just eating big sandwiches. The others bring out their potential investor, Simon Cowell. Scooby and Shaggy take the opportunity to poorly sing “Shallow” (which Simon dislikes, naturally) before the rest of the gang gets down to business. While Simon is impressed with Fred’s leadership, Velma’s smarts, and Daphne’s style, he thinks Scooby and Shaggy are the weak links, and he can’t invest in Mystery Inc. Dejected, Scooby and Shaggy ditch the gang.

The guys go to their favorite bowling alley where they lament the feeling that they are considered useless among the gang. Soon, they are attacked when the pins and balls turn into deadly little robots called Rottens. They chase Scooby and Shaggy around the place until they end up in the back of the place and are sucked up into the sky by a spacecraft. Meanwhile, Fred, Velma, and Daphne are driving back feeling bad about Scooby and Shaggy before they overhear the police scanner talking about the bowling alley incident, and they rush on over there.

Scooby and Shaggy find themselves inside the Falcon Fury, Blue Falcon’s super jet. They are greeted by Dee Dee Skyes (Kiersey Clemons) and is brought up to meet Blue Falcon himself. However, Dynomutt (Ken Jeong) comes out to reveal that it’s actually Blue Falcon’s adult son Brian (Mark Wahlberg), who has taken over his dad’s position after he retired, but Dynomutt clearly feels like he is working with an amateur. Dee Dee tells the guys that the robots were sent by the fiendish Dick Dastardly (Jason Isaacs), who is seeking out the Three Skulls of Cerberus, the ancient three-headed dog, but nobody knows for what purpose. They also don’t know why the robots were going after Scooby and Shaggy. Dastardly and his minions then attack the Fury, but Dee Dee manages to get them away from him by flying them out of there in hyperdrive. Brian then suggests that Scooby and Shaggy stick around for the mission so that they may be able to stop Dastardly.

Fred, Daphne, and Velma talk to the lady at the bowling alley about the incident and are given one of the robots that got crushed and left behind. Velma inspects it and finds one of Dastardly’s hairs on it. After putting it in a scanner, the gang learns of Dastardly and his mission to collect the Skulls. As they head off to find their friends, Velma also learns of how Dastardly has been going through a database of dogs, and the reason that he wants Scooby is because he is the last descendant of Peritas, dog of Alexander the Great, and that he could be the key to something big. Fred then drives them toward Dastardly Demolition so that they might be able to find Dastardly himself.

Brian says he got the location of the second skull from an anonymous fan. They arrive at an amusement park, only to find that Dastardly is there and that he’s already gotten the skull. He sends his Rottens after the heroes. When he finds Scooby and Shaggy, he makes it clear that he has no interest in Shaggy and blasts him through the wall before trying to get Scooby. The dog runs into a house of mirrors, but Dastardly finds him and tries to convince him of his great destiny. Scooby gets away with help from Dynomutt, and the heroes return to the Fury before losing Dastardly from their tails. However, the robot that the gang is holding reactivates and alerts Dastardly to its whereabouts.

The gang is still driving on Fred’s “shortcut” before they are pulled over by an attractive officer (Christina Hendricks), who turns out to be Dastardly in disguise. He uses the Rottens to kidnap the gang and also pull the Mystery Machine into his ship. They are imprisoned aboard but are freed when they find a Rotten whose head was pulled off and replaced with a dust vacuum. Daphne gives it a clean head, and it joins their side. They overhear Dastardly plotting a course for the location of the third skull, Messick Mountain.

The other heroes start treating Scooby as more essential to the mission, which leaves Shaggy feeling left out. Scooby even gets a costume, which meant having to take off his beloved collar. Moments later, Velma manages to hack into Dynomutt’s system to deliver a message to Dee Dee about heading to Messick Mountain. Dastardly catches the gang and cuts off their connection. Daphne then asks him about the dog that he has a shrine to – Muttley (Billy West). Dastardly reveals his true intentions: He and Muttley were trying to open the portal to the underworld to steal the treasures from there, but he made Muttley go in alone, and although he was able to enter, he couldn’t come out since he was not the “key”. Therefore, Muttley remained trapped in the underworld, and Dastardly is trying to get him back. He has the Rottens re-imprison Velma and Daphne before taking Fred for himself.

The heroes arrive on Messick Mountain and enter Mystery Island, but they leave Shaggy behind on the Fury, and he shows clear resentment toward Scooby. On their travels, they meet Captain Caveman (Tracy Morgan). He is keeping the third skull, which he calls a “Slaghoople”, and challenges the gang to fight him so they can take it. He wipes the floor with Brian, but they are supposedly saved when Shaggy arrives with what appears to be Fred having driven the Mystery Machine to the ship. This is really Dastardly in disguise, and he knocks Captain Caveman out to grab the skull and Scooby. Shaggy reunites with the real gang and feels responsible for Scooby getting captured. He gives a rousing speech to the gang, plus Brian, Dee Dee, and Dynomutt, and they all agree to go save Scooby together.

Dastardly puts the skulls together and opens the portal to the underworld, transforming the town into an ancient appearance. As the heroes close in, he has the Rottens attack them, but Dynomutt stops the Mystery Machine from crashing as it’s blown out of the sky. Dastardly uses Scooby’s paw to open the gates and unleash Cerberus. Dastardly realizes he’s made a mistake and he runs from the giant, but then runs back through the gates to find Muttley. He appears dead at first, but the rascal was just joking, and the two villains proceed to pilfer the treasures.

Scooby frees his friends from the busted Mystery Machine, but Fred is distraught at the loss of the beloved van. They then proceed to plan to get Cerberus back through the gates. The good Rotten rounds up his friends and they join the gang in their plan. Brian then decides to pull off his big hero moment by saving Scooby from Cerberus by punching the heads repeatedly. The Rottens turn into bowling balls while the others distract Cerberus and trip him up, sending him rolling back into the underworld. Fred then takes out a clue he stole from Dastardly’s ship, which Velma reads and determines means that only Scooby and Shaggy can close the portal, but there’s a catch: one of them has to stay behind in the underworld to keep it closed. Scooby and Shaggy try to stop one another from making the sacrifice, but ultimately, Shaggy decides to do it. They close the portal, but Scooby is sad at losing his best friend. The others comfort him until they realize that Alexander the Great did come up with a way to see his friend (Peritas) again. A statue of Alexander and Peritas appears with an inscription he created. Scooby reads it and re-opens the portal. Cerberus kicks Shaggy out and returns him to Scooby, where they embrace, and Shaggy gives Scooby his collar back. The Rottens then turn on Dastardly and Muttley, giving them to Brian and Dee Dee to take into custody.

The gang opens up a Mystery Inc shop to expand their business, and Brian presents them with a brand new Mystery Machine. They get a call for another mystery and head off on their next big case.

The credits show other Hanna Barbers characters like Jabberjaw and Magilla Gorilla joining on missions while Muttley helps Dastardly break out of prison.

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Scooby-Doo and Shaggy become best friends as kids before meeting Fred, Daphne, and Velma, and devoting their lives to solving mysteries. The fiendish Dick Dastardly wants to use Scooby and the three skulls of the ancient dog Cerberus to open the gates to the underworld to free his old friend Muttley and steal the treasures within. Scooby and Shaggy team up with their hero, the Blue Falcon (actually his son Brian) plus Dynomutt and Dee Dee Skyes to stop Dastardly.

Dastardly kidnaps Fred, Daphne, and Velma, who learn of his true plans. After he gets all the skulls, Dastardly opens the portal and unleashes Cerberus. He and Muttley go after the treasures, while the heroes send Cerberus back inside, but the prophecy states that a man and dog who are best friends must close the portal with one of them staying behind. Shaggy chooses to stay behind, but they soon find an inscription that Scooby reads to bring Shaggy home. Dastardly and Muttley are then taken into custody by Brian and his team.

The gang expands its Mystery Inc business and continues to solve mysteries.