The effect of climate change on crop production and nitrate-nitrogen (NO3-N) pollution from subsurface drained fields is of a great concern. Using the calibrated and validated RZWQM2 (coupled with CERES-Maize and CROPGRO in DSSAT), the potential effects of climate change and elevated atmospheric CO2 concentrations (CO2) on tile drainage volume, NO3-N losses, and crop production were assessed integrally for the first time for a corn-soybean rotation cropping system near Gilmore City, Iowa. RZWQM2 simulated results under 20-year observed historical weather data (1990–2009) and ambient CO2 were compared to those under 20-year projected future meteorological data (2045–2064) and elevated CO2, with all management practices unchanged. The results showed that, under the future climate, tile drainage, NO3-N loss and flow-weighted average NO3-N concentration (FWANC) increased by 4.2 cm year−1 (+14.5 %), 11.6 kg N ha−1 year−1 (+33.7 %) and 2.0 mg L−1 (+16.4 %), respectively. Yields increased by 875 kg ha−1 (+28.0 %) for soybean [Glycine max (L.) Merr.] but decreased by 1380 kg ha−1(−14.7 %) for corn (Zea mays L.). The yield of the C3 soybean increased mostly due to CO2enrichment but increased temperature had negligible effect. However, the yield of C4 corn decreased largely because of fewer days to physiological maturity due to increased temperature and limited benefit of elevated CO2 to corn yield under subhumid climate. Relative humidity, short wave radiation and wind speed had small or negligible impacts on FWANC or grain yields. With the predicted trend, this study suggests that to mitigate NO3-N pollution from subsurface drained corn-soybean field in Iowa is a more challenging task in the future without changing current management practices. This study also demonstrates the advantage of an agricultural system model in assessing climate change impacts on water quality and crop production. Further investigation on management practice adaptation is needed.