Nitrogen (N) loss is a significant source of water quality pollution in alluvial watersheds. However, the mechanisms linking N loss and elevated CO2 concentration (eCO2) are not well recognized. In this study, we comprehensively calibrated the SWAT model equipped with a dynamic CO2 input and response module to investigate the response mechanisms between multiform N losses and eCO2 in a representative large‐scale watershed. Results revealed nitrate loss under eCO2 exceeding 100% in some upstream zones under the SSP5‐8.5 scenario (P < 0.05) compared to the constant CO2 concentration. This was directly related to the great increase in hydrological variables, which were the carriers of N losses, and the intensive inputs of N fertilizer. Results also found that nitrate leaching was greater than the other two processes for future periods, peaking at 309.3%, as compared to the baseline period. The findings suggested reducing fertilizer inputs by 10%–20% was promising, especially for reducing nitrate loss through runoff and leaching by up to 17.7% and 12.2%. This study explored the mechanisms of increased N loss in response to eCO2 and provided scientific evidence for early warning and making decisions to improve water quality at a large watershed scale.