Green Cove Springs is named after a local warm mineral spring. There is evidence the area has seen human use for as much as 7,000 years but modern development in the are didn't begin until the King of Spain granted land to George E. Clarke to build a sawmill in 1816. The town itself was established in 1854 as White Sulphur Springs, then renamed Green Cove Springs in 1866.

Green Cove Springs was an agricultural area until the Great Freeze of 1895 wiped out the citrus crop. An it never came back. However, Green Cove Springs is also home to the main farm of Gufstafson's Farm, a privately owned brand of milk and dairy products sold throughout Florida.