Jesse Montgomery III (Ashton Kutcher) and Chester Greenburg (Seann William Scott) are two laid-back friends who awaken at Jesse's residence, suffering from a hangover and a complete blackout of the previous evening's events. Their fridge is inexplicably filled with chocolate pudding, and an angry message from their girlfriends, Wilma (Marla Sokoloff) and Wanda (Jennifer Garner), is waiting on the answering machine, expressing their frustration about the boys' mysterious disappearance. As the duo steps outside, they quickly realize that Jesse's car is nowhere to be found, along with the gifts meant for their significant others' anniversary. This shocking revelation prompts Jesse to exclaim:
> "Dude, where's my car?"
Desperate to discover its location—especially since the twins have promised them a "special treat," which they hope will lead to some romantic time—the two friends embark on a zany adventure to retrace their steps from the previous night.
Their first stop is at their friend Nelson's (David Herman) house, where they engage in a hilariously absurd discussion about recovering their memories while watching Nelson's dog get high on cannabis. After that, they venture to an outrageous drive-through Chinese restaurant called Chinese Foooood, where the irate cashier (Freda Foh Shen) repeatedly annoys Jesse by asking, "and then?" causing him to lose his cool and wreak havoc at the order speaker.
The plot thickens when they bump into Christie Boner (Kristy Swanson), the local attractive girl who recognizes them and mentions an unforgettable night they had, which leads to confrontation with her overprotective boyfriend Tommy (Charlie O'Connell) and his gang. Their adventures take a wild turn at the Kitty Kat Club, a strip joint where they're well-acquainted with the staff. Here, Jesse has an unexpected encounter with Tania (Teressa Tunney), who reveals that he had been entrusted with a suitcase filled with stolen cash, and demands its return.
As their misadventures unfold, Jesse and Chester decide to check in at their girlfriends' place to try jogging their memories. Unfortunately, their erratic behavior results in chaos as they accidentally spill trash everywhere, leading to the twins kicking them out. Things take a strange turn when they are abducted by a group of space aficionados led by the eccentric Zoltan (Hal Sparks). They learn about a mysterious and powerful device called the Continuum Transfunctioner, which they unwittingly possessed the previous night.
When they finally regain their freedom, Jesse and Chester are taken to a tailor (Keone Young) who presents them with stylish suits. They discover strange tattoos on their backs—Jesse's says "Dude," and Chester's reads "Sweet." They further unearthed gadgets such as cell phones and a rented convertible sports car which deepen the mystery surrounding their chaotic night.
Before long, they encounter five stunning women donned in tight black outfits known as the Hot Chicks, who are also on the hunt for the Continuum Transfunctioner. The plot thickens as these two groups of aliens collide with our protagonists, both aiming to claim the device capable of cosmic destruction. Following a series of wild miscommunications and misunderstandings, Jesse and Chester find themselves at the police station, mistaken for criminals, where they learn their vehicle was impounded.
As the story unfolds, the stakes rise dramatically when their old friends and their significant others get involved. In a climactic showdown at Captain Stu’s Space-O-Rama—a local mini-golf and arcade—the men finally understand that the key to saving the universe rests in solving a Rubik's Cube, which Chester has unconsciously fiddled with. Each twist of the cube not only reveals more about their lost night but also inches them closer to averting the destruction of their beloved world.
In a final attempt to save the universe, the boys rely on cunning and the knowledge gained from watching wildlife documentaries. Chester remarkably activates the device that turns out being their salvation. In the end, with universe-saving antics, mind erasure, and heartfelt connections, Jesse, Chester, and their girlfriends find some semblance of normalcy as they set off for dinner in Jesse's car, obliviously unaware of the cosmic chaos that just unfolded—all while debating the meanings of their newly etched tattoos.
