Although a wealth of research documents the interactions between climate, land use, vegetation, and fire in the Ozarks over the last 300 years, little is known about these interactions at longer timescales. Here, the Holocene vegetation and fire history of the Ozarks is reviewed based on pollen and charcoal records from Cupola Pond (Smith 1984; Jones et al. 2017) and Sweeton Pond (Nanavati and Grimm 2019). The high-resolution data from Sweeton Pond are compared to dendroecological records to understand the role of climate and fire in shaping local vegetation history for the last 2000 years. The influence of people, particularly the Osage Native Americans, are assessed from historical accounts and archaeological studies. The dominance of oak-hickory forest in this region began ~15,000 BP following a marked decline in boreal taxa. Between 10,000 and 5000 BP, high abundance of grass pollen and low abundances of forest taxa, suggest a savannah-like landscape near Cupola Pond during the warm, dry middle Holocene. Oak-hickory forest returned to Cupola Pond from 5000 to 2000 BP and was followed by increased pollen abundance from shortleaf pine and water tupelo at the expense of oak, suggesting the local establishment of swamp-forest with effectively wet conditions. At Sweeton Pond, pollen and charcoal data indicate open oak-hickory forest and frequent low-severity fires, suggesting interannual climate variability as a driver of vegetation and fire occurrence. Between 590 and 130 BP (1360-1820 CE), mesic, fire-sensitive taxa expanded in conjunction with cool, effectively wet conditions. Despite climate conditions that were seemingly less favorable for fire, the expansion of the Osage Native Americans in the region was accompanied by more fire and a late increase in fire-dependent shortleaf pine between ~450 and 130 BP (1500-1820 CE). The expansion of both fire-sensitive and fire-dependent taxa coincident with Osage occupation of the area suggest that anthropogenic fire and land use were local in nature and increased landscape heterogeneity prior to Euro-American settlement. Since 1820 CE increased Euro-American settlement, agriculture, and logging in the area are evidenced by large increases in disturbance taxa at the expense of shortleaf pine. During this period, forest clearance led to fuel fragmentation, reducing fire activity; after 1920 CE, fire was actively suppressed.