Willis Robertson was born in Martinsburg, West Virginia to Franklin P. Robertson and Josephine Ragland (Willis) Robertson and he graduated from the University of Richmond in 1907. Robertson was elected to the Virginia State Senate as a Democrat in 1915 and he served from 1916 to 1922. Robertson served in the United States Army during World War I. Robertson served as Commonwealth Attorney for Rockbridge County, Virginia from 1922 to 1928.

Robertson was elected to the House of Representatives in 1932. He served from 1933 until he resigned in 1946 to enter the United States Senate. Robertson had a typically socially conservative Southern Democrat voting record and he was the chairman of the U.S. Senate Committee on Banking, Housing, and Urban Affairs from 1959 until 1966. Robertson served in the Senate from 1946 until 1967. In 1956, Robertson was one of the 19 senators who signed The Southern Manifesto, condemning the U.S. Supreme Court decision in Brown vs. Board of Education and the resulting public desegregation. When President Lyndon Johnson sent the First Lady on a train trip through the South to encourage support for the Civil Rights and Voting Rights Acts, Sen. Robertson was one of four Southern Senators who refused to meet with her on the whistle stop trip. In retaliation, President Johnson arranged to unseat him. He was defeated for renomination in 1966 and resigned on December 30, 1966. He was one of the architects of the Southern Strategy utilized by presidential candidate Richard Nixon in 1968, and a mainstay of Republican election strategy to this day.

Willis' best known son is televangelist Pat Robertson.