Background: Along the prairie-forest border in the south-central USA exists one of the most extensive areas of uncut forest in the nation (>323,750 hectares), providing unique potential for developing multi-century records of environmental changes through dendrochronological analyses. Twentieth century changes in vegetation, increased prescribed fire management, and recent years of elevated wildfire activity have increased interest in understanding the region’s long-term fire regime characteristics. To address this need, we analyzed and compared fire intervals, seasonality, severity, and extent based on fire-scar history datasets from three new and ten existing study sites. Results: At the study sites, mean fire intervals ranged from 3 to 10 years prior to Euro-American settlement and generally became more frequent after. The majority of fires occurred in the dormant season and resulted in low percentages of trees scarred. Coinciding with Euro-American settlement (EAS), fire frequencies appear to have varied by geography. At the regional scale, fire regimes have trended towards decreased fire severity and slightly decreased fire intervals over the past 300 years. Further, fires appear to have increased in extent from circa 1770 to the mid to late 1800s, after which it began to decline, circa 1920. Conclusions: Although frequent, descriptions of fire regimes since the eighteenth century should be characterized as time-dependent and spatially variable, likely depending on local socio-ecological influences. Similar influences may explain fire frequency increases following EAS, while fire severity trended lower.