Researchers have debated the relative importance of environmental versus Indigenous effects on past fire regimes in eastern North America. Tree-ring fire-scar records (FSRs) provide local-resolution physical evidence of past fire, but few studies have spatially correlated fire frequency from FSRs with environmental and anthropogenic variables. No study has compared FSR locations to Native American settlement features in the eastern United States. We assess whether FSRs in the eastern US are located near regions of past Native American settlement. We also assess relationships between distance to Native American settlement, environmental conditions, and fire frequency in central Pennsylvania (PA), US, using an “ensemble of small models” approach for low sample sizes. Regression models of fire frequency at 21 locations in central PA often selected distance-based proxies of Indigenous land use. Models with mean annual temperature and Native American variables as predictors explained > 70% of the variation in fire frequency. Alongside temperature and wind speed, “distance to nearest trail” and “mean distance to nearest town” were significant and important predictors. In 18th-century central PA, fires were more frequent near Indigenous trails and towns, and further south due to increasing temperature and pyrophilic vegetation. However, for the entire eastern US, FSRs are located far from past settlement, limiting their effectiveness in detecting fire patterns near population centers. Improving understanding of historical fire will require developing FSRs closer to past Native American settlement.