He served in Florida's House of Representatives. In 1978 he was elected a lieutenant governor of state (deputy governor) to governor Bob Graham. They were reelected in 1982. Mixson served as lieutenant governor from 1979 to 1987. During his second term he was also state Secretary of Commerce. In 1987, Graham resigned from office to become U.S. Senator. Mixson was sworn in as governor for three days, from January 3 to January 6, when governor-elect Robert Martinez (Rep.) took over.
During the 2004 presidential election, Mixson crossed party lines to endorse the re-election of President George W. Bush. Now he is co-chair state senator Rod Smith (Dem.) campaigning for governor in 2006.
- "John Wayne Mixson". Florida Governors Mansion. http://www.floridagovernorsmansion.com/the_people_s_house/former_residents/john_wayne_mixson. Retrieved 10 February 2013.