In this study, the potential future changes of mean and extreme precipitation in the middle and lower Yangtze River basin (MLYRB), eastern China, are assessed using the models of phase 5 of the Coupled Model Intercomparison Project (CMIP5). Historical model simulations are first compared with observations in order to evaluate model performance. In general, the models simulate the precipitation mean and frequency better than the precipitation intensity and extremes, but still have difficulty capturing precipitation patterns over complex terrains. They tend to overestimate precipitation mean, frequency, and intensity while underestimating the extremes. After correcting for model biases, the spatial variation of mean precipitation projected by the multimodel ensemble mean (MME) is improved, so the MME after the bias correction is used to project changes for the years 2021–50 and 2071–2100 relative to 1971–2000 under two emission scenarios: RCP4.5 and RCP8.5. Results show that with global warming, precipitation will become less frequent but more intense over the MLYRB. Relative changes in extremes generally exceed those in mean precipitation. Moreover, increased precipitation extremes are also expected even in places where mean precipitation is projected to decrease in 2021–50. The overall increase in extreme precipitation could potentially lead to more frequent floods in this already flood-prone region.