Regional assessments of the impacts of climate change on both human systems and the natural environment require high-resolution projections to see the effects of global-scale change on the local environment. This project sought to address a critical and generally overlooked assumption inherent to these projections of regional, multi-decadal climate change: that the statistical relationship between global climate model simulation outputs and real, observed climate data remain constant over time. Utilizing a “perfect--‐model” experimental design and the output of two high-resolution global climate model simulations, this study evaluated and reported on the ability of three different methods to simulate current and future temperature and precipitation in the U.S., with a focus on the southern Great Plains region. Differences between the methods’ abilities during the late 20th versus late 21st century time periods can provide valuable information regarding the level of confidence we should attribute to the climate projections commonly used in impacts analyses and as the basis for decision-support and planning purposes.