Crop residue is potentially a major biomass feedstock for bio-based industries. Spatial and interannual variability of crop residue yield potential in relation to climatic variability in average of daily mean temperature and total precipitation during crop growing season at regional scale has not previously been investigated. Crop yield data were used to estimate crop residue yield potential and quantify its spatial and temporal variability across the North Central Region of the USA. A correlation analysis was also conducted to examine the relationship between temporal stability of crop residue yield and climatic variability. Temporal variability in crop residue and climate parameters was quantified by the coefficient of variation (CV). Based on this observational study, the counties in the south- eastern part of the North Central Region were observed to have relatively stable crop residue yield potential and also have a relatively low CV of average of daily mean temperature and total precipitation during the crop growing season. The CV of crop residue yield potential was positively correlated with the CVs of average of daily mean temperature and total precipitation. These findings highlight the influences of climatic variability on the spatial and temporal patterns of crop residue yield potential, and emphasize that these factors should be taken into account when developing regional strategies for sustainable bioenergy production.