When stressed by low soil water content (SWC) or high vapor pressure deficit (VPD), plants close stomata, reducing transpiration and photosynthesis. However, it has historically been difficult to disentangle the magnitudes of VPD compared to SWC limitations on ecosystem-scale fluxes. We used a 13 year record of eddy covariance measurements from a forest in south central Indiana, USA, to quantify how transpiration and photosynthesis respond to fluctuations in VPD versus SWC. High VPD and low SWC both explained reductions in photosynthesis relative to its long-term mean, as well as reductions in transpiration relative to potential transpiration estimated with the Penman-Monteith equation. Flux responses to typical fluctuations in SWC and VPD had similar magnitudes. Integrated over the year, VPD fluctuations accounted for significant reductions of GPP in both nondrought and drought years. Our results suggest that increasing VPD under climatic warming could reduce forest CO2 uptake regardless of changes in SWC