Studies were conducted to determine if herbicide metabolism is an additional mechanism that could explain the resistance of ACCase- and ALS-resistant grain sorghum to quizalofop and rimsulfuron, respectively. ACCase- and ALS-resistant and -susceptible genetic lines were grown under controlled conditions and treated at the 4-leaf stage with 14 C-labeled quizalofop and rimsulfuron. Plants were harvested at 3, 5, and 7d after treatments. In the ACCase metabolism experiment, resistant grain sorghum transformed 88% of quizalofop-ethyl to quizalofop while 91% of the inactive was converted to active form by the susceptible plants 3DAT. By 7DAT, all inactive quizalofop-ethyl was converted to active quizalofop. In the ALS metabolism study, two distinct metabolites were produced from rimsulfuron. Metabolism rate was similar between resistant lines (TX430R and N223R) in all harvest dates except at 7 DAT; however, more rapid metabolism were observed when resistant were compared with the susceptible genotypes (TX430S and N223S). The percentage of recovered rimsulfuron 3DAT corresponded to 80% and 83% in the resistant compared to 87% in the susceptible grain sorghum. At 5DAT, metabolism was near steady in all sorghum plants but by 7DAT, resistant genotypes metabolized 4–12% more than the susceptible sorghum. Metabolism of rimsulfuron in ALS-resistant grain sorghum is an added mechanism that could help elevate the level of rimsulfuron resistance.