Despite the importance of the Yellow River to China, climate change for the middle reaches of the Yellow River Basin (YRB) has been investigated far less than for other regions. This work focuses on future changes in mean and extreme climate of the YRB for the near-term (2021–2040), mid-term (2041–2060), and far-term (2081–2100) future, and assesses these with respect to the reference period (1986–2005) using the latest REgional MOdel (REMO) simulations, driven by three global climate models (GCMs) and assuming historical and future [Representative Concentration Pathway (RCP) 2.6 and 8.5] forcing scenarios, over the CORDEX East Asia domain at 0.22° horizontal resolution. The results show that REMO reproduces the historical mean climate state and selected extreme climate indices reasonably well, although some cold and wet biases exist. Increases in mean temperature are strongest for the far-term in winter, with an average increase of 5.6 °C under RCP 8.5. As expected, the future temperatures of the warmest day (TXx) and coldest night (TNn) increase and the number of frost days (FD) declines considerably. Changes to mean temperature and FD depend on elevation, which could be explained by the snow-albedo feedback. A substantial increase in precipitation (34%) occurs in winter under RCP 8.5 for the far-term. Interannual variability in precipitation is projected to increase, indicating a future climate with more extreme events compared to that of today. Future daily precipitation intensity and maximum 5-day precipitation would increase and the number of consecutive dry days would decline under RCP 8.5. The results highlight that pronounced warming at high altitudes and more intense rainfall could cause increased future flood risk in the YRB, if a high GHG emission pathway is realized.