Many of the present day issues associated with fire management in wilderness areas are addressed by studying past interactions among fire, humans, vegetation and climate. In this paper we describe three centuries of the fire regime in the Lower Buffalo River Wilderness Area, Arkansas, USA. We reconstructed fire events from 159 tree-ring dated fire scars on 26 shortleaf pine (Pinus echinata Mill.) remnants and live trees. During the late-17^th Century and early 18^th Century the mean fire return interval (MFI) was 7.7 y. Fire frequency increased abruptly circa 1820 with fires burning every 2 y on average until 1920. The number of fires decreased during the 1900s as cultural values changed to favor fire suppression over multiple-use burning. Analyses of the influence of human ignitions and drought on the fire regime resulted in two important findings: (1) that fire frequency was positively correlated to human population density up to 1920 and (2) the influence of drought seemed to be masked by frequent anthropogenic fires and fire suppression. Fire events were associated with droughts only prior to Euro-American settlement. Studies of climate-fire relationships should consider the potential for anthropogenic influence and future studies should attempt to quantify the historic role of humans in the fire regime.