Beavis and Butt-Head wake up to discover their TV has been stolen, setting off on a nationwide journey to retrieve it. In their search, they accidentally wind up in a hotel where they get caught up in the plans of a shady criminal named Muddy Grimes. Mistaken for hitmen, Beavis and Butt-Head are tasked by Muddy to "do" his wife, Dallas, and sent on a cross-country bus ride, imagining all along that they are going to "score." The duo barely grasps what's truly expected of them, believing they are destined for romantic escapades. Their antics unwittingly involve them in an intrigue involving biological warfare.

As they travel across the country, Beavis and Butt-Head repeatedly find themselves at odds with law enforcement, including federal agents led by the persistent Agent Flemming. Misunderstandings escalate as they visit iconic American landmarks and create chaos wherever they go, frequently crossing paths with both Muddy and Dallas. Totally oblivious to the mayhem they are causing and the manhunt tailing them, their misadventures result in nationwide panic. With much of the authorities now convinced they pose an imminent threat to national security, the boys continue to bumble their way toward the conclusion of their misadvised quest, consistently clueless about the magnitude of their predicament or the greatly inflated national drama surrounding them.