The 2000 United States Senate election in Tennessee took place on November 7, 2000, as part of the general election including the 2000 U.S. presidential election, elections to the House of Representatives and various state and local elections. Incumbent Republican U.S. Senator Bill Frist won re-election to a second term, defeating Democratic candidate Jeff Clark.

William Harrison Frist is an American physician, businessman, conservationist and policymaker who served as a United States Senator from Tennessee from 1995 to 2007. A member of the Republican Party, he also served as Senate Majority Leader from 2003 to 2007. Born in Nashville, Tennessee, Frist studied government and health care policy at Princeton University and earned a Doctor of Medicine degree from Harvard Medical School. He trained as a cardiothoracic transplant surgeon at Massachusetts General Hospital and Stanford University School of Medicine, and later founded the Vanderbilt Transplant Center. In 1994, he defeated incumbent Democratic Senator Jim Sasser.