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Climate change impacts food production systems, particularly in locations with large, vulnerable populations. Elevated greenhouse gases (GHG), as well as land cover/land use change (LCLUC), can influence regional climate dynamics. Biophysical factors such as topography, soil type, and seasonal rainfall can strongly affect crop yields. We used a regional climate model derived from the Regional Atmospheric Modeling System (RAMS) to compare the effects of projected future GHG and future LCLUC on spatial variability of crop yields in East Africa. Crop yields were estimated with a process-based simulation model. The results suggest that: (1) GHG-influenced and LCLUC-influenced yield changes are highly heterogeneous across this region; (2) LCLUC effects are significant drivers of yield change; and (3) high spatial variability in yield is indicated for several key agricultural sub-regions of East Africa. Food production risk when considered at the household scale is largely dependent on the occurrence of extremes, so mean yield in some cases may be an incomplete predictor of risk. The broad range of projected crop yields reflects enormous variability in key parameters that underlie regional food security; hence, donor institutions strategies and investments might benefit from considering the spatial distribution around mean impacts for a given region. Ultimately, global assessments of food security risk would benefit from including regional and local assessments of climate impacts on food production. This may be less of a consideration in other regions. This study supports the concept that LCLUC is a first-order factor in assessing food production risk.