There were significant differences for LRP1B, FLT4, FBXW7, RNF43, ATRX, APC and PIK3CA mutation frequencies in early-onset non-hypermutated CRCs between racial/ethnic groups. Heterogeneities by race/ethnicity were observed for the effect of APC, FLT4 and FAT1 between early-onset and late-onset non-hypermutated CRC. By sex, heterogeneity was observed for the effect of EP300, BRAF, WRN, KRAS, AXIN2 and SMAD2. Males and females with non-hypermutated CRC had different trends in EP300 mutations by age group. These findings define genomic patterns of early-onset non-hypermutated CRC by race/ethnicity and sex, which yields novel biological clues into early-onset CRC disparities.