Best friends Jesse and Chester awaken with hangovers and no memory of the previous night. The television is on, showing an Animal Planet program about how animals use twigs and rocks as tools to get food. Their refrigerator is filled with containers of chocolate pudding, and the answering machine contains an angry message from their twin girlfriends Wilma and Wanda as to their whereabouts. They emerge from their home to find Jesse’s car missing, and with it their girlfriends’ first-anniversary presents. The two were also fired from their jobs. This prompts Jesse to ask the film’s titular question: “Dude, where’s my car?”
Because the girls have promised them a “special treat”, which Jesse and Chester take to mean sexual intercourse, the men are desperate to retrieve their car. The duo begins retracing their steps in an attempt to discover where they left the car. Along the way, they encounter a transgender stripper, a belligerent speaker box operator at a Chinese restaurant’s drive-through (voiced by Freda Foh Shen), two tattoos they discover on each other’s backs, UFO cultists led by Zoltan (who later hold the twins hostage), a Cantonese-speaking Chinese tailor, the Zen-minded Nelson and his cannabis-loving dog Jackal, the attractive Christie Boner, her aggressive jock boyfriend Tommy and his friends, a couple of hard-nosed police detectives, and a reclusive French ostrich farmer named Pierre. They also meet two groups of aliens, one group being five gorgeous women, the other being two Norwegian men, searching for the “Continuum Transfunctioner”: an extraterrestrial device that the boys accidentally picked up last night.
After Pierre releases the duo for correctly answering a question about ostriches, Jesse and Chester head over to a local arcade named Captain Stu’s Space-O-Rama. Once inside, they encounter Zoltan and his cultists who give them Wilma and Wanda in exchange for a toy that Jesse and Chester try to pass off as the Transfunctioner. Tommy, Christie, and the jocks arrive along with Nelson and his dog, whom they release after Tommy snatches the fake Transfunctioner from Zoltan. The two sets of aliens arrive and notify of the real Continuum Transfunctioner: a Rubik’s Cube that Chester has been working hard to solve, and eventually does, causing the device to shapeshift into its true form. They are warned that once the five lights stop flashing, the universe will be destroyed.
Jesse and Chester must determine which of two sets of aliens is entitled to the device. One of the groups is there to protect the universe, the other is there to destroy it. Both claim to be the protectors of the universe, stating that they were with Jesse and Chester the previous night, which Jesse and Chester still cannot remember, and ask for the Transfunctioner. The two correctly choose the men, because when the men were asked what they did the night before, they correctly respond that they got a hole in one at the 18th hole at the arcade’s miniature golf park, and won a lifetime supply of pudding. At the last second, they deactivate the Transfunctioner, saving the universe.
Thwarted, the five alien women merge to become a beautiful giantess clad in a purple bra and miniskirt. She devours Tommy alive in front of Christie, who reacts with indifference. The giantess then crawls out of the amusement center and chases Jesse and Chester. The cultists tell them to activate the Photon Accelerator Annihilation Beam on the Transfunctioner. However, the button that activates it is too far in to reach. At the last second, Chester remembers the nature show with the tool-using chimps and uses a straw to push the recessed button, thus destroying the alien. Tommy survives, but Christie breaks up with him in favor of Nelson. The protectors thank Jesse, Chester and the twins for saving the world, and erase their minds concerning the events. The protectors park the duo’s car, a Renault Le Car, behind a mail truck for them to find the following morning. Jesse and Chester salvage their relationships with the twins and discover the special treat from the girls turns out to be matching berets with Jesse and Chester’s names knitted in the front. The protectors leave a gift for their girlfriends (and, for the two men): Breast Enhancement Necklaces. The film ends with Jesse, Chester, and the twins going in Jesse’s car out for Chinese food while arguing what the tattoo said on each other’s back.