Chiles was re-elected to the U.S. Senate twice, in 1976 and 1982. Chiles, never flashy, was considered a moderate lawmaker who rarely made waves. He served as the Chairman of the Special Committee on Aging of the 96th Congress (1979–1981), and in the 100th Congress (1987–1989) served as chairman of the influential Senate Budget Committee. While heading the Budget Committee, he played a key role in the 1987 revision of the Gramm-Rudman-Hollings Act.
Chiles underwent quadruple-bypass heart surgery in 1985. After his recovery, he became increasingly frustrated with the slow pace of work in the Senate, complaining that it was too difficult to get anything done. He announced in December 1987 that he would not seek re-election the next year. Chiles was succeeded by Republican Connie Mack.