Spinosad is a commercial reduced-risk pesticide that is naturally derived. Spinosad’s performance was evaluated on four classes of wheat (hard red winter, hard red spring, soft red winter, and durum wheats) against adults of the lesser grain borer, Rhyzopertha dominica (F.); rice weevil, Sitophilus oryzae (L.); sawtoothed grain beetle, Oryzaephilus surinamensis (L.); red flour beetle, Tribolium castaneum (Herbst); and larvae of the Indianmeal moth, Plodia interpunctella (Hübner). Beetle adults (25) or P. interpunctella eggs (50) were exposed to untreated wheat and wheat treated with spinosad at 0.1 and 1 mg (AI)/kg of grain. On all untreated wheat classes, adult beetle mortality ranged from 0 to 6%, and P. interpunctella larval mortality ranged from 10 to 19%. The effects of spinosad on R. dominica and P. interpunctella were consistent across all wheat classes. Spinosad killed all exposed R. dominica adults and significantly suppressed progeny production (84–100%) and kernel damage (66–100%) at both rates compared with untreated wheat. Spinosad was extremely effective against P. interpunctella on all wheat classes at 1 mg/kg, based on larval mortality (97.6–99.6%), suppression of egg-to-adult emergence (93–100%), and kernel damage (95–100%), relative to similar effects on untreated wheats. The effects of spinosad on S. oryzae varied among wheat classes and between spinosad rates. Spinosad was effective against S. oryzae, O. surinamensis and T. castaneum only on durum wheat at 1 mg/kg. Our results suggest spinosad to be a potential grain protectant for R. dominica and P. interpunctella management in stored wheat.