He served in Florida's House of Representatives. In 1978 he was elected a lieutenant governor (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 Bob Martinez (Rep.) took over.