Senator Connie Mack III and cancer prevention advocate Ludie Priscilla (née Hobbs).

[7] In 2000, incumbent Republican State Representative Debby Sanderson decided to retire to run for a seat in the Florida Senate.

[10] In 2003, incumbent Republican Congressman Porter Goss announced his intention to retire in order to serve as Director of the CIA.

That October, Mack resigned from the Florida Legislature and moved back to his hometown of Fort Myers to run for his father's old seat.

Mack stated, "The people of the 14th District deserve to be represented in Washington by someone who shares our mainstream conservative Republican values in the mold of my father and Congressman Porter Goss".

He voted against George W. Bush's domestic eavesdropping program in 2006 and Foreign Intelligence Surveillance Act Reform in 2007.

[18] Mack was an outspoken critic of late Venezuelan President Hugo Chávez,[19] as well as one of the most vocal opponents of the Latin American television network teleSUR.

As a member of the Transportation and Infrastructure Committee, Mack helped secure over $81 million to expand Interstate 75 in Southwest Florida, a project of significant concern to the region.

[22] On October 26, 2011, it was announced Mack had changed his mind and that he would seek the Republican nomination because he felt no one in the current field was able to defeat Nelson.

[28][29] In December 2020, Mack joined Platinum Advisors DC to lobby in support of increased humanitarian assistance to Ethiopia.

[31] In 1992, Mack was involved in a bar fight with professional baseball player Ron Gant in Georgia.