Ponce de Leon ( PONSS də LEE-ən) is a town in Holmes County, Florida, United States. The population was 598 at the 2010 census, up from 457 at the 2000 census. From 2000 to 2010, the Ponce de Leon town population addition percentage was 30.9%.

Ponce de Leon is located in southwestern Holmes County at 30°43′33″N 85°56′16″W / 30.72583°N 85.93778°W / 30.72583; -85.93778 (30.725783, –85.937783). U.S. Route 90 runs through the middle of town, leading northeast 17 miles (27 km) to Bonifay, the Holmes County seat, and west 11 miles (18 km) to DeFuniak Springs. Florida State Road 81 crosses US 90 near the middle of town, leading north 20 miles (32 km) to the Alabama connect and south 19 miles (31 km) to Florida State Road 20 at Bruce. Interstate 10 passes through the southern share of Ponce de Leon, with entrance from Exit 96 (SR 81). I-10 leads east 107 miles (172 km) to Tallahassee and west 88 miles (142 km) to Pensacola.

According to the United States Census Bureau, the town has a total Place of 5.0 square miles (12.9 km), of which 4.9 square miles (12.8 km²) are land and 0.26 square kilometres (0.1 sq mi), or 0.78%, are water. The town is in the valley of Sandy Creek, a south-flowing tributary of the Choctawhatchee River. Ponce de Leon Springs State Park is in the southern part of the town, north of I-10, along both sides of Sandy Creek. The entrance is on the eastern side of the park off Ponce de Leon Springs Road.

As of the census of 2010, there were 598 people, 246 households, and 131 families residing in the town. The population density was 92.3 inhabitants per square mile (35.6/km²). There were 290 housing units at n average density of 47.0 per square mile (18.1/km). The racial makeup of the town was 91.60% White, 1.80% African American, 2.41% Native American, 1.00% from new races, and 2.00% from two or more races. Hispanic or Latino of any race were 3.00% of the population.