AbstractMinimizing forest vulnerability to more frequent and severe droughts, as climate models predict, has emerged as a primary goal of forest management. One potential strategy to moderate drought‐induced stress is reducing basal area through the repeat application of prescribed fire. However, use of prescribed fire as a management tool to reduce drought vulnerability has been largely untested. Here, we report the long‐term effects of repeat fires on the climate‐growth response of adult oaks (Quercus spp.) in the Missouri Ozarks, USA. We measured the annual radial growth of trees that experienced either no fire, periodic (every 4 yr), or annual prescribed fires from 1950 to 2015. To assess whether increased fire frequency interacts with climate to determine long‐term forest productivity, we modeled annual growth as a function of potential evapotranspiration, fire treatment, and their interaction. We also quantified the effect of fire‐driven reductions in tree density on carbon and oxygen isotope composition of tree rings and drought resistance (growth during drought) and resilience (growth recovery after drought) during past drought events. Annual radial growth and isotopic composition data indicated trees experienced reduced growth due to moisture stress, but drought vulnerability did not vary between frequently burned forests and unburned controls. In contrast, periodic, but not annual, fires reduced annual growth by 9.6% during wet periods favorable to growth with the effect consistent over time. Fire had minimal effects on total and inorganic soil nitrogen after 65 yr of treatment, regardless of frequency, suggesting other underlying causes of the observed growth declines under periodic burning (e.g., crown, bole, or root injury). Our results suggest that long‐term, increased fire frequency can have negative effects on long‐term tree growth, but effects are contingent upon the fire return interval. These findings highlight important differences in how fire and thinning influence density‐dependent competition and the response of tree growth to climate. Although additional studies are needed from other forest ecosystems, this study provides early evidence that increased fire frequency will not alleviate drought stress and instead, may reduce long‐term, aboveground carbon storage in forests.