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Abstract Lakes support globally important food webs through algal productivity and contribute significantly to the global carbon cycle. However, predictions of how broad‐scale lake carbon flux and productivity may respond to future climate are extremely limited. Here, we used an integrated modeling framework to project changes in lake‐specific and regional primary productivity and carbon fluxes under 21st century climate for thousands of lakes. We observed high uncertainty in whether lakes collectively were to increase or decrease lake CO₂emissions and carbon burial in our modeled region owing to divergence in projected regional water balance among climate models. Variation in projected air temperature influenced projected changes in lake primary productivity (but not CO₂emissions or carbon burial) as warmer air temperatures decreased productivity through reduced lake water volume. Cross‐scale interactions between regional drivers and local characteristics dictated the magnitude and direction of lake‐specific carbon flux and productivity responses to future climate.