Sullivan attended Washington University and was a teacher and director at St. Louis Comptometer school. She was married to John B. Sullivan who served four terms in Congress, and she served as his administrative aide. Following her husband's death in 1951, she served as an aide to Congressman Leonard Irving until she left to run for Congress herself in 1952. She was re-elected eleven times. In Congress, she served for many years as Secretary of the House Democratic Caucus.
She did not seek re-election in 1976, and was succeeded by Dick Gephardt. The former Wharf Street in front of the Gateway Arch in Downtown St. Louis was renamed Leonor K. Sullivan Boulevard in her honor.