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The film opens with a Spartan elder inspecting three babies. The first, an ugly, talking baby ogre (Shrek the Third), is abandoned to die for its deformity; while the second, who is Vietnamese, is adopted by Brad Pitt and Angelina Jolie. The third, Leonidas, is accepted as a Spartan for his already-present muscular physique and prepared for kinghood through brutal training. An adult Leonidas (Sean Maguire) is cast out into the wild, survives the harsh winter, and hunts down a gangsta penguin (Happy Feet). Returning a king for his inauguration wearing a penguin skin hat, Leonidas sees Margo (Carmen Electra) erotically dancing and asks her to marry him, to which she responds by giving him the combination to her chastity belt.

Years later, Leonidas is training his son when Captain (Kevin Sorbo) informs him that a Persian messenger has arrived. Accompanied by the Spartan politician Traitoro, the messenger presents Xerxes' demands for Sparta's submission. After growing angry with both the messenger's disrespect and finding him making out with his wife, Leonidas kicks him into the "pit of death". Despite Traitoro's advice that the messenger's guards are now needed to convey the actual message, Leonidas kicks them in as well, along with several other people he simply dislikes. Resolving to face the Persians, Leonidas visits the prophets and gives them medicines such as Neutrogenaas their prize for their consultation. They advise him that he should consult the Oracle for any advice. The Oracle, Ugly Betty, reveals that Leonidas will die should he go to war.

After reaching a decision while spending the night with his wife, Leonidas meets the soldiers assembled for his departure to Thermopylae, and finds that only thirteen were accepted in the army due to stringent requirements. Among them are Captain, his son Sonio, and a slightly unfit Spartan named Dilio. Once at the Hot Gates, they encounter a deformed Paris Hilton (also played by Parker), who tells Leonidas and the Captain about a secret goat path above the Hot Gates that Xerxes could use to outflank the Spartans. When she asks to be made a Spartan soldier, Leonidas rejects her as unqualified due to her inability to use a spear correctly. Leonidas and his platoon soon face off with Xerxes' messenger and his Immortals, beating them in a dance contest before driving them off a cliff. Xerxes (Ken Davitian), impressed, personally approaches Leonidas and attempts to bribe him with a trip to the Palms Hotel and Casino. Leonidas declines, and the Spartans face the Persian army in a "Yo Momma" fight, which the Spartans win, but Dilio has his eyes scratched out and wanders away.

Hilton decides to betray the Spartans and reveals the location of the goat path to Xerxes in return for various gifts and for having her deformed hump removed. Xerxes meets the twelve remaining Spartans and the war begins. Meanwhile, back in Sparta, Queen Margo has several confrontations with Traitoro, as he is the vital vote in sending more troops to assist her husband. Following her address to the Council, Traitoro publicly betrays the Queen. The Queen then battles Traitoro in a parody of Spider Man 3 and defeats him using a dust buster. With Traitoro's deceit exposed, the council is united with the queen.

At the Battle of Thermopylae, the Persians introduce their secret weapons, Ghost Rider and Rocky Balboa, who kills Sonio with a decapitating uppercut. Captain avenges him with Botox poisoning before being struck down by Xerxes. Leonidas pursues Xerxes and plays Grand Theft Auto. Managing to find the "Transformer Cube", Xerxes uses it in a car to become Xerxestron and shows off his powers to access the "Leave Britney Alone!" video on YouTube. However, Xerxestron accidentally trips on his extension cord and falls on Leonidas and the surviving Spartans, apparently killing them. The blind Dilio eventually returns to Sparta to tell of Leonidas' final moments. A year later, Dilio leads a larger Spartan force to defeat the Persians, but the blind warrior ends up going the wrong way. They end up in Malibu, where they knock Lindsay Lohandown as she is leaving rehab again.

The film begins at a truck stop in an unspecified rural location. It is night time in the midst of a heavy rainstorm, and a hooker gets into a large, black Peterbilt and offers her "services" to the trucker inside. The trucker is revealed to be Rusty Nail (Mark Gibbon) when he recites his phrase "I like the rain. Keeps everybody inside and washes everything clean." He asks the hooker to go out into the rain to get wet. When she is unnerved by this strange behavior and states she is leaving, Rusty Nail locks the doors and tells her to leave through the open window. He then shuts the window halfway as she is clambering out, trapping her with half her body hanging outside the truck. Rusty Nail then drives off, decapitating the hooker as he drives alongside a trailer attached to a truck.

Meanwhile, Melissa and her fiancé Bobby (Nicki Aycox and Nick Zano), a young engaged couple in their early twenties, are on a cross country road trip in a 1983 Chevrolet Caprice Wagon. They are heading across the Southwestern United States to Las Vegas, where they plan on getting married. Joining them for the ride is Melissa's sister Kayla (Laura Jordan), who along the way picks up her online boyfriend Nik (Kyle Schmid), a punk.

When their car breaks down in the desert, the four find a seemingly abandoned house along a side road. In the barn, they find a silver 1971 Chevrolet Chevelle in working order with the gas tank fully filled. Melissa and Bobby are initially reluctant to take the car, as it amounts to thieving, but due to Kayla and Nik's persistence, they relent. However, Melissa leaves a note in the house with her contact details for whomever may own the house and/or car.

The next day, Melissa receives a phone call from the person who owned the car they stole. He then calls Melissa "Goldilocks" (she is blonde), revealing that he can see her. He also tells her, "I believe you have something of mine, 'cause I now have something of yours," soon after Bobby disappears from a diner restroom. The others find a CB radio in their car, with which Rusty Nail talks to them. He orders them to destroy their cellphones and follow his orders if Bobby is to survive, and he has some quite nasty psychological mind games that create a bridge for gory, life-and-death situations. The group continues to follow Rusty Nail, who promises them that they will be all reunited soon, after Rusty requests for Kayla's middle finger, a reference to when Kayla flipped off the driver of a truck who turned out to be Rusty. The group cuts a finger from a corpse and reach the wrong trucker because Rusty already knew that they had broken the rules. Rusty cuts one finger off Bobby and puts it in the glove compartment of the vehicle, which is eventually discovered by the group.

Rusty later instructs Melissa to "strip down to her underwear" in front of his truck; it turns out not to be him, but some other trucker named Kenny Chesney whom Rusty Nail had instructed to be there. Rusty Nail soon pulls up at a bar in Utah, and Bobby tries to escape. He gains the attention of the barman, who has gone outside to smoke, but Rusty Nail catches him and uses a chainsaw-chain to cut off the barman's jaw. He then commands Nik to walk through a party dressed as a female and to buy crystal meth. Nik refuses to do this, and Melissa takes a knife to his throat, whereupon Nik cries, confessing that he is scared and his tattoos are fake. Nik walks up to the party in the clothes that were seen on the hooker earlier, only for Rusty to kidnap Nik and drive off. Melissa and Kayla chase them, and in the ensuing car chase, Rusty manages to ram their car several times, overturning it. Kayla's leg is pinned, and she is killed when Rusty rams again, causing the car to explode.

Rusty takes Bobby and Nik back to his home and has them play a sadistic game of "Craps" with dice. In this game, whatever one person rolls makes the other person suffer. Bobby's kneecap is struck by a hammer and his nipple branded by the letter R. Once Bobby rolls a double one snake eyes, Rusty kills Nik by stabbing him with a steel bar through the top of his head. Melissa breaks into a police station and steals a motor bike, racing off to find Bobby. Rusty Nail hangs Bobby by his neck in the back of his truck. Melissa parks the police motorcycle by the side of the truck, distracting Rusty and allowing her to overpower the killer with a few well-placed hits to the back with a shovel. She drives away in his truck, accidentally disconnecting the cabin from the rest of the truck and leaving Bobby behind, but Rusty manages to grab on to the side of the truck and climb on the roof. Melissa drives until the sun comes up and ends up plowing into a gas tank, causing the truck to catch fire. Melissa jumps from the truck as Rusty takes control, but it's too late, and he drives off the side of a cliff, the truck exploding on impact. Bobby escapes from the trailer and meets back up with Melissa, their ordeal finally over.

Later, in the middle of nowhere, a girl is stuck on the side of the road because her car has broken down. A big red Peterbilt truck with a trailer attached drives past her, only to stop and back up after she makes a nasty comment. She explains what's happened and asks for a ride. As the truck door opens, it is revealed that the driver has a badly burnt right arm. The girl climbs in and a familiar voice says "You'll catch your death out there," revealing that the driver is Rusty Nail, who survived the explosion. He drives away with the girl.