Large changes in atmospheric CO2, temperature and precipitation are predicted by 2100, yet the long-term consequences for carbon, water, and nitrogen cycling in forests are poorly understood. We applied the PnET-CN ecosystem model to compare the long-term effects of changing climate and atmospheric CO2 on productivity, evapotranspiration, runoff, and net nitrogen mineralization in current Great Lakes forest types. We used two statistically downscaled climate projections, PCM B1 (warmer and wetter) and GFDL A1FI (hotter and drier), to represent two potential future climate and atmospheric CO2 scenarios. To separate the effects of climate and CO2, we ran PnET-CN including and excluding the CO2 routine. Our results suggest that, with rising CO2 and without changes in forest type, average regional productivity could increase from 67% to 142%, changes in evapotranspiration could range from –3% to +6%, runoff could increase from 2% to 22%, and net N mineralization could increase 10% to 12%. Ecosystem responses varied geographically and by forest type. Increased productivity was almost entirely driven by CO2 fertilization effects, rather than by temperature or precipitation (model runs holding CO2 constant showed stable or declining productivity). The relative importance of edaphic and climatic spatial drivers of productivity varied over time, suggesting that productivity in Great Lakes forests may switch from being temperature to water limited by the end of the century.