Landscape-scale prescribed burning may be appealing for natural community restoration due to operational efficiency and possible heterogeneity in fire effects across broad spatial scales. We monitored plant community responses for >15 years with variable prescribed fire frequencies applied across a Missouri Ozarks landscape stratified into distinct ecological site types. Through the study period, burning had no effect on the overstory tree density or basal area. Midstory stem densities decreased rapidly in periodically burned units and more gradually with annual fire. Burning increased total ground flora cover and the cover of forbs, grasses, and legumes. The effect of burning on species richness differed among site types, with increased species richness through time on exposed slopes. There was no effect of prescribed burning on species richness on two of three protected slope site types, and annual burning decreased species richness in upland waterways. Among the site types, the upland waterways had the most species associated with pre-burn communities. We conclude that (i) burning consistently increased cover of ground layer vegetation across the landscape, while decreasing the midstory stem densities, and (ii) site type moderated ground flora richness response, with more pronounced effects of prescribed burning on exposed sites than on protected sites.