Brantley County was formed from parts of Charlton, Pierce and Wayne counties as a result of a state constitutional amendment passed by Georgia voters on November 2, 1920.  There is some controversy over exactly who the county was named after.  The state historical marker on the grounds of the Brantley County courthouse and several other sources indicate the county was named for Benjamin D. Brantley who was a member of a prominent local family.  Other sources claim the name honored Benjamin Brantley's son, William Goodman Brantley of Brunswick, Georgia who served as a state representative, state senator and eight term U.S. Representative.

Since the Okefenokee Swamp is to the south and west of the county, passage through Brantley County was essential to railroads running from the coast through the southern part of the state. 

There are two Forts located in Brantley County; Fort McIntosh and Fort Mudge.  Fort McIntosh was built in the early years of the American Revolutionary War to protect the large herds of cattle.  It was placed under siege from Tories in 1777 and eventually surrendered.  For Mudge was built about the same time and was immortalized by Walt Kelly in the "Pogo" comic strip.