In 1940, Harris was elected as United States Representative for Arkansas's 7th congressional district, which in 1950 was redistricted to , encompassing the southern portion of the state. He served without interruption for more than twenty-five years, from January 3, 1941, until February 2, 1966. He was the chairman of the Subcommittee on Legislative Oversight of the Committee on Interstate and Foreign Commerce, where in 1959 he presided over hearings on the "quiz show scandal." In the 1960s, Harris was the chairman of the Committee on Interstate and Foreign Commerce (Eighty-fifth through Eighty-ninth Congresses). He was the lead House sponsor of the Kefauver Harris Amendment, an amendatory act to the federal Pure Food and Drug Act, the law that mandates that pharmaceutical companies disclose the side effects of medications approved by the United States Food and Drug Administration for sale in the United States.