In 1942, after G. Lloyd Spencer decided not to seek re-election, McClellan ran for the Senate again and this time won. He served as senator from Arkansas from 1943 to 1977, when he died in office. During his tenure, he served as chairman of the Appropriations Committee and served 22 years as chairman of the Committee on Government Operations. McClellan was the longest serving United States Senator in Arkansas history. During the later part of his Senate service, Arkansas had, perhaps, the most powerful Congressional delegations with McClellan as chairman of the Senate Appropriations Committee, Wilbur Mills as chairman of the House Ways and Means Committee, Oren Harris as chairman of the House Commerce Committee, Senator J. William Fulbright as chairman of the Senate Foreign Relations Committee, Took Gathings as chairman of the House Agriculture Committee, and James William Trimble as a member of the powerful House Rules Committee.