Mathews was appointed to the United States Senate on January 2, 1993 by then Gov. Ned McWherter to fill the seat vacated by newly elected Vice President Al Gore. He stepped down from office on December 1, 1994, upon the election of Fred Thompson, who later resumed his acting career and is now a candidate for the presidency of the United States.
Mathews, now 80, was a longtime associate of McWherter, serving in his administration both as deputy governor and as state treasurer. He also served in the administrations of governors Gordon Browning, Frank G. Clement, and Buford Ellington.