The book for which Thompson gained most of his fame had its genesis during the research for Strange Rumblings in Aztlan, an exposé for Rolling Stoneon the 1970 killing of the Mexican-American television journalist Rubén Salazar. Salazar had been shot in the head at close range with a tear gas canister fired by officers of the Los Angeles County Sheriff's Department during the National Chicano Moratorium March against the Vietnam War. One of Thompson's sources for the story was Oscar Zeta Acosta, a prominent Mexican-American activist and attorney. Finding it difficult to talk in the racially tense atmosphere of Los Angeles, Thompson and Acosta decided to travel to Las Vegas, Nevada, and take advantage of an assignment bySports Illustrated to write a 250-word photograph caption on the Mint 400 motorcycle race held there.
What was to be a short caption quickly grew into something else entirely. Thompson first submitted to Sports Illustrated a manuscript of 2,500 words, which was, as he later wrote, "aggressively rejected." Rolling Stone publisher Jann Wenner was said to have liked "the first 20 or so jangled pages enough to take it seriously on its own terms and tentatively scheduled it for publication — which gave me the push I needed to keep working on it", Thompson later wrote.
The result of the trip to Las Vegas became the 1972 book Fear and Loathing in Las Vegas which first appeared in the November 1971 issues of Rolling Stone as a two-part series. It is written as a first-person account by a journalist named Raoul Duke on a trip to Las Vegas with Dr. Gonzo, his "300-pound Samoan attorney", to cover a narcotics officers' convention and the "fabulous Mint 400". During the trip, Duke and his companion (always referred to as "my attorney") become sidetracked by a search for the American Dream, with "...two bags of grass, seventy-five pellets of mescaline, five sheets of high-powered blotter acid, a salt shaker half full of cocaine, and a whole galaxy of multi-colored uppers, downers, screamers, laughers and also a quart of tequila, a quart of rum, a case of Budweiser, a pint of raw ether, and two dozen amyls."
Coming to terms with the failure of the 1960s countercultural movement is a major theme of the novel, and the book was greeted with considerable critical acclaim, including being heralded by the New York Times as "by far the best book yet written on the decade of dope". "The Vegas Book", as Thompson referred to it, was a mainstream success and introduced his Gonzo journalism techniques to the masses.