The setting for the film is late 1950s America, a time during which television was rapidly replacing radio as the most popular entertainment medium. Although Rhodes is coarse and abusive, he possesses a colloquial, on-air charm that quickly endears him to the hearts and minds of rural listeners after Marcia Jeffries (Neal), a small-town radio personality, discovers him in the county jail of the fictional town of Pickett, in northeast Arkansas, and lands him a radio show there. A talent scout invites him to appear on television in Memphis, Tennessee, where Rhodes is introduced to Mel Miller (Matthau), a bookish Vanderbilt graduate who writes his scripts. However, Rhodes makes a name for himself by insulting his sponsor to the delight of his adoring audience. Rhodes's sponsor, the "Luffler Mattress" company, is offended but forced to relent in canceling the show when they discover Rhodes's antics are actually increasing their sales (and that the wife of owner Luffler is a Lonesome Rhodes fan). An opportunistic "office boy" (portrayed by Anthony Franciosa) lands Rhodes a contract in New York City, where he becomes the national TV spokesman for Vitajex, an innocuous dietary supplement.
A frenetic montage of Rhode's hyperbolic ads for Vitajex is one of the film's most memorable sequences, revealing the gullibility of the American public to a persuasive con-artist. In the tradition of classical tragedy, Rhodes is undone by his thirst for power and by Jeffries who, despite building his stardom, becomes so fed up that she allows him to expose his contempt for his fans on the air. As a "Cracker Barrel" broadcast ends, Rhodes is shown, with sound off and an announcer doing a voiceover, smiling and waving to the camera as he speaks contemptuously of his audience. In the control room, Jeffries and the technical staff hear him continue to mock his viewers as "idiots," "morons," "guinea pigs. " Fed up with Rhodes' betrayal, aware she helped create the monster, Jeffries pushes slide switches that throw Rhodes's comments on the air.
In minutes, furious, betrayed fans who heard the remarks are calling the network. In a symbolic moment, an unaware Rhodes's popularity is shown plummeting as he rides an elevator down following the show. The film ends with a meltdown at Rhodes's penthouse apartment, as Jeffries admits she betrayed him and Matthau predicts his future, that he'll return to the air but it won't be quite as fancy. An uncredited Rip Torn is shown at one point as "Barry Mills," the next young Lonesome Rhodes waiting in the wings. Interviewed for the DVD release in 2006 and the documentary accompanying the film, Griffith, Neal and Franciosa all express pride in their work in the film, and Schulberg explains the film's origins..