Cagle was the 11th lieutenant governor of Georgia and the first Republican to hold the office in Georgia's history. On July 18, 2006, Cagle defeated conservative political activist Ralph Reed in the 2006 Republican primary for the seat. Cagle defeated Democrat Jim Martin on November 7, 2006.

In 2010, Cagle won re-election with over 54% of the vote against Carol Porter (D) and David Barber (L) in the general election.

Cagle sought a third term in 2014. He was unopposed for the Republican nomination in the May 20 primary and faced Democrat Connie Stokes in the general election. He won the general election on November 4, 2014.

As lieutenant governor, Cagle also served as president of the Georgia State Senate.

In 1994, Cagle ran for the Georgia State Senate in the 49th District. He defeated the Democratic incumbent, Jane Hemmer, and became the youngest member of the state Senate at age 28. He was re-elected to the seat five times. He served as chairman of the State Senate Finance Committee.