Background: Traditional polyethylene film mulching is widely used in the Loess Plateau region of China to improve crop yields. However, whether long-term polyethylene film mulching can continue to ensure crop yield under future climate change conditions is questionable. First, we conducted a four-year field experiment to calibrate and validate the biogeochemical DeNitrification–DeComposition (DNDC) model. Then, based on the calibrated and validated model, we evaluated the spring maize yield and water use efficiency under different film mulching methods (no mulching, traditional polyethylene film mulching, and biodegradable film mulching) in the Loess Plateau region. Results: The temperature and rainfall in the Loess Plateau region are predicted to increase in the future (2021–2100) under four scenarios due to higher CO2 concentrations. Through 252 simulation results, we found that future climate change will have positive impacts under no mulching, traditional polyethylene film mulching, and degradable film mulching conditions. The yield increase will be greater with no mulching, but in the future, film mulching will continue to reduce crop yields. Additionally, the crop yield reduction under traditional polyethylene film mulching is greater. A sensitivity analysis indicated that rainfall will have a major effect on yield, and polyethylene film mulching will reduce the sensitivity of the yield to rainfall. As the rainfall increases, the differences between the yield and water use efficiency under ordinary plastic film and degradable film will become smaller. In the later period with a warmer and wetter climate under the SSP585 scenario, the water use efficiency will be higher under degradable film than traditional polyethylene film mulching. Conclusion: It can be seen that degradable film is more adaptable to the warmer and wetter climate in the future.