Fort White, Florida was constructed in 1836 as a military fort during the Second Seminole War. The purpose of the fort was to protect the Cow Creek Settlement. Supplies were brought up the Santa Fe River by steamboat and were distributed from Fort White to other nearby forts and settlers. The actual site of the fort was located about four (4) miles west of the current town on the Santa Fe River. The fort was abandoned on June 26, 1842 due to illness among the troops. There are no remains of the fort visible today.

The town was incorporated in 1884 still named after the military fort. After the arrival of the railroad in 1888, the town started to grow due to such industries as phosphate mining, turpentine production, and agricultural crops of cotton, trees, and oranges. The town quickly grew to a population of 2,000 but declined once again in 1896 and 1897 due to the harsh winters which destroyed the citrus industry. 

By 1910, the largest phosphate deposits were depleted, and mining ceased. The boll weevil ended cotton farming before World War I which saw the population shrink to a few hundred people mostly consisting of ranchers, farmers, and foresters.