Raoul Duke and his attorney Dr. Gonzo drive a red convertible across the Mojave desert to Las Vegas with a suitcase full of drugs to cover a motorcycle race. As their consumption of drugs increases at an alarming rate, the stoned duo trash their hotel room and fear legal repercussions. Duke begins to drive back to L.A., but after an odd run-in with a cop, he returns to Sin City and continues his wild drug binge.

In Los Angeles, a gang of bank robbers who call themselves The Ex-Presidents commit their crimes while wearing masks of Reagan, Carter, Nixon and Johnson. Believing that the members of the gang could be surfers, the F.B.I. sends young agent Johnny Utah to the beach undercover to mix with the surfers and gather information.