After Governor Swanson's term ended, he began to look for some position in politics, but none seem available. Then, most unexpectedly, John W. Daniel, one of Virginia's U.S. Senators, died in office. Claude was appointed to fill the unexpired term. He was later confirmed in that position by the legislature, and then he won popular election to the position in 1916, 1922 and 1928.
He served as chairman of the Committee on Public Buildings and Grounds in the Sixty-third through Sixty-fifth Congresses. In the Sixty-fifth and Sixty-sixth sessions he served on committees overseeing Naval matters. He resigned before the end of his last term in order to take the position of Secretary of the Navy under President Franklin D. Roosevelt.
In 1919 Senator Swanson was one of President Wilson's strongest supporters in pressing for the League of Nations. He opened debate in the Senate on the subject and worked tirelessly toward accommodation on the League. However America's isolationism was not yet ready to accept the concept of the League of Nations.
During his time in the Senate, Claude Swanson became one of the leading Capital Hill experts on Naval affairs. President Herbert Hoover, a Republican, appointed him to serve as a Delegate to the General Disarmament Conference being held in Geneva, Switzerland, beginning on February 2, 1939.