James F. Byrnes High School was built in 1955 at a cost of $1,000,000. At that time, there were 21 teachers and 500 students in grades 9-12. In 1969, students in grades 10-12 attended Byrnes and all ninth grade students attended Florence Chapel School (D. R. Hill Annex). In 1971, the ninth grade moved back to J. F. Byrnes High School. In 2007, the ninth grade moved to a separate facility. The James F. Byrnes Freshman Academy is located at the former D. R. Hill Middle School. Presently there are 1650 students served by 141 faculty and staff members. There are approximately 600 students in the Byrnes Freshman Academy.
Additions and renovations to Byrnes were made in 1962, 1979, 1990, 1993, 1995, 1999, 2002, 2004, 2007, and 2009.