With increasing concerns about the impact of warming temperatures on water resources, more attention is being paid to the relationship between runoff and precipitation, or runoff efficiency. Temperature is a key influence on Colorado River runoff efficiency, and warming temperatures are projected to reduce runoff efficiency. Here, we investigate the nature of runoff efficiency in the upper Colorado River (UCRB) basin over the past 400 years, with a specific focus on major droughts and pluvials, and to contextualize the instrumental period. We first verify the feasibility of reconstructing runoff efficiency from tree-ring data. The reconstruction is then used to evaluate variability in runoff efficiency over periods of high and low flow, and its correspondence to a reconstruction of late runoff season UCRB temperature variability. Results indicate that runoff efficiency has played a consistent role in modulating the relationship between precipitation and streamflow over past centuries, and that temperature has likely been the key control. While negative runoff efficiency is most common during dry periods, and positive runoff efficiency during wet years, there are some instances of positive runoff efficiency moderating the impact of precipitation deficits on streamflow. Compared to past centuries, the 20th century has experienced twice as many high flow years with negative runoff efficiency, likely due to warm temperatures. These results suggest warming temperatures will continue to reduce runoff efficiency in wet or dry years, and that future flows will be less than anticipated from precipitation due to warming temperatures.