Fran Kranz stars as Joel, a guy who has recently been dumped by his girlfriend (on the advice of an abusive television therapist Dr. Dwayne, played by Darrell Hammond), sending him into a spiral of depression. His two friends, Wyatt (Kenan Thompson) and Ben (Zachary Levi), a closeted gay man, take him on a road trip to lift his spirits and take revenge on Dr. Dwayne. The friends take their trip in Wyatt's van, which he has customized into a cross-country hotdog stand called the weinerwagon in an attempt to impress Oscar Mayer and get a job with them.
On the way, they encounter an elderly nymphomaniac couple Frank and Felicia Applebaum (Blake Clark and Mindy Sterling) who had sexual intercourse in front of them. After being dropped off, Mr Applebaum says "Next time bring Da noise or Da Funk" and does a break dance in front of them. they realized their wallets are stolen by three women, leaving them with only ten dollars delivered to Wyatt in a 15-year-old birthday card from his grandmother. They use this money to enter into a hot bod contest, on which Ben had a flashback of his mother constantly yelling at him to work hard in the competition. After getting advice from a man named Walrus Boy, he wins, getting $10,000 for the prize.
As they approach their destination, Joel abandons his friends in a fit of hopelessness, winding up drunk in a back alley. His childhood tormenter, Drake Hanswald (Andy Milonakis), appears in a hallucination, and Joel watches helplessly as his younger self is tormented by Drake and all of his other classmates. Realizing that he needs to change his situation and stand up for himself, Joel returns to his friends just in time to save them from the hippies who had previously stolen Wyatt's hood ornament.
The next morning, they go to the studio where Dr. Dwayne's show is filmed and sneak in. After beating up Dr. Dwayne's decoy, the real Dr. Dwayne appears, revealing that he intentionally caused Joel's breakup to motivate Joel to take a stand for himself. He also reveals that he has found a rich man that Wyatt had saved from a life of drugs, who is willing to finance Wyatt's Wieners. Ben makes a speech to the audience and accepts his homosexuality.
Now that the friends have all achieved what they needed, they head home, and we learn that Wyatt's Wieners became the 4th most successful pre-packaged meat company in the U.S. and that he lives in a hotdog-shaped house with his dachshund named Beyoncé. Ben went on to become a successful lawyer and cologne designer, and that he currently lives with his "roommate" Johnathan and his two cats. Joel invented "unpantsable" pants, and the three friends take the Wienerwagon on a road trip every year to spread cross-country happiness.