;U.S. House elections Mack made his first run for public office in 1982, when he ran in the Republican primary for the 13th District, a newly created district centered around Fort Myers. The old 13th, represented by Democrat William Lehman, had been renumbered as the 17th district. Mack led the field in a crowded four-way Republican primary with 28 percent of the vote, and won a run-off election in October against State Representative Ted Ewing 58% to 42%. In the November general election, he won with 65% of the vote. In 1984, he won re-election unopposed and in 1986 won with 75% of the vote. ;1988 U.S. Senate election Incumbent Democratic U.S. Senator Lawton Chiles decided to retire. After three terms in the U.S. House, Mack decided to run for the U.S. Senate. He won the primary with 62% of the vote against Robert Merkle. In the general election, he defeated Democratic U.S. Congressman Buddy Mackay with just 50% of the vote. ;1994 U.S. Senate election In the general election, he defeated Democratic attorney Hugh Rodham 71% to 29%. He won every county in the state. He was the only Republican Senator in Florida history to get elected to more than one term until Marco Rubio did so in 2016.
Tenure
During his congressional career, Mack supported the passage of laws dealing with health care, financial modernization, modification of the tax code, and public housing reform. A cancer survivor, Mack has also been a strong advocate for cancer research, early detection and treatment Mack led a historic bipartisan congressional effort to double funding for biomedical research through the National Institutes of Health and worked to secure the necessary appropriations. He also secured Medicare coverage for clinical trials, and was a leading Republican advocate of the Women's Health Initiative. He worked to strengthen and reform the U.S. Food and Drug Administration. Mack helped define the framework of landmark legislation to allow the financial industry to respond appropriately to the increasing demands of an aggressive global marketplace. He has worked to reduce gov't debt. He co-authored and introduced into the House the landmark Gramm-Rudman deficit reduction law. Mack was also instrumental in passage of the Everglades Restoration Act, which was signed into law on December 11, 2000. He decided to retire in 2000 rather than run for re-election to a third term. Democrat Bill Nelson, the Florida State Treasurer and a former U.S. Representative, won the open seat. Mack's son, U.S. Congressman Connie Mack IV, ran unsuccessfully against Nelson in 2012.
1992, he received the American Cancer Society's Courage Award and the Susan G. Komen Breast Cancer Foundation's Betty Ford Award.
Post-congressional career
In 2005, Connie Mack III was appointed by President George W. Bush as Chairman of the President's Advisory Panel for Federal Tax Reform. Since early 2007, Mack III has served as the Senior Policy Advisor to Liberty Partners of Tallahassee, a Florida-based lobbying firm. On April 15, 2010, Mack resigned as campaign chairman for Charlie Crist's race for the U.S. Senate.
Representation in other media
In 2005, Mack was featured in , a documentary about the development of Cape Coral. His father Connie Mack, Jr. had worked as a public relations man for Leonard and Jack Rosen, the brothers who developed Cape Coral as a resort waterfront. The producer interviewed Connie Mack III at his Palm Island home in Florida.
