We investigated the effects of a combination of protease, xylanase, and phytase in maize- or sorghum-based diets for broilers. Two experiments were conducted with male chicks randomly distributed in a 3 × 2 factorial arrangement with three replacement levels of maize with sorghum (0%, 50%, and 100%) with or without enzymes. In the first trial, 1152 chicks were allotted to 36 floor pens to determine performance, relative organ weight, and litter moisture. A second trial was performed with 150 and 120 chicks allotted in 30 cages with five and four broilers per cage to determine nutrient and energy utilization from 11 to 21 d and from 25 to 35 d, respectively. Enzyme supplementation improved body-weight gain and feed conversion ratio. Total maize replacement with sorghum compromised body-weight gain from 1 to 14 d and from 1 to 35 d. Nitrogen retention was reduced by partial and total maize replacement with sorghum at starter phase and by total replacement at grower phase. Enzyme supplementation improved nitrogen retention at starter phase and apparent metabolizable energy at starter and grower phases. Therefore, partial maize replacement with sorghum is viable and on top application of an enzyme blend containing protease, xylanase, and phytase improves performance and nutrient retention of broilers.