The effects of soil variability on regional crop yield under projected climate change are largely unknown. In Southeastern Norway, increased temperature and precipitation are projected for the mid-21st century. Crop simulation models in combination with scaling techniques can be used to determine the regional pattern of crop yield. In the present paper, the CSM-CROPSIM-CERES-Wheat model was applied to simulate regional spring wheat yield for Akershus and Østfold counties in Southeastern Norway. Prior to the simulations, parameters in the CSM-CROPSIM-CERES-Wheat model were calibrated for the spring wheat cvars Zebra, Demonstrant and Bjarne, using cultivar trial data from Southeastern Norway and site-specific weather and soil information. Weather input data for regional yield simulations represented the climate in 1961–1990 and projections of the climate in 2046–2065. The latter were based on four Global Climate Models and greenhouse gas emission scenario A1B in the IPCC 4th Assessment Report. Data on regional soil particle size distribution, water-holding characteristics and organic matter data were obtained from a database. To determine the simulated grain yield sensitivity to soil input, the number of soil profiles used to describe the soilscape in the region varied from 76 to 16, 5 and 1. The soils in the different descriptions were selected by arranging them into groups according to similarities in physical characteristics and taking the soil in each group occupying the largest area in the region to represent other soils in that group. The simulated grain yields were higher under all four projected future climate scenarios than the corresponding average yields in the baseline conditions. On average across the region, there were mostly non-significant differences in grain yield between the soil extrapolations for all cultivars and climate projections. However, for sub-regions grain yield varied by up to 20% between soil extrapolations. These results indicate how projected climate change could affect spring wheat yield given the assumed simulated conditions for a region with similar climate and soil conditions to many other cereal production regions in Northern Europe. The results also provide useful information about how soil input data could be handled in regional crop yield determinations under these conditions.