Before the 1900s, the Chipola was a typical Florida sandhills site, with an overstory of longleaf pine trees, a midstory of scattered scrub oaks, and an understory of grasses and other herbaceous plants. Most of the longleaf pines on the site were logged in the 1900s, leaving only a few scattered patches and isolated trees. By the 1950s, when the experimental forest was established, most of the upland sites had been taken over by scrub oak and wiregrass.

Until 1981, Forest Service and cooperator research was conducted through a unit based in Marianna, FL. After the unit was closed in 1982, the 2,760-acre experimental forest was reduced to 1,250 acres, then reduced again in the 1990s. In 2004, SRS purchased the 940 acres that currently make up the Chipola.

Early research on the Chipola included species comparison trials on various conifers, including Choctawhatchee sand pine, a native pine species growing almost exclusively in northwest Florida and extreme southeast Alabama. Findings showed that only Choctawhatchee sand pine and longleaf pine can be grown successfully on the deep sand soils that typify the sandhills. Almost all of the current knowledge on how to establish and manage Choctawhatchee sand pine comes from research on the experimental forest.

In the 1990s, land managers in the Florida Panhandle area noted a large decline in wiregrass—a dominant understory plant in the longleaf pine ecosystem—due to mechanical site preparation methods. SRS research plant ecologist Kenneth Outcalt used the research plots on the Chipola to address these concerns and to make specific recommendations to reduce soil disturbance and wiregrass mortality.