A 4×2 factorial feeding trial was designed to investigate the effect of replacing soybean meal (SBM) with cottonseed meal (CSM) in wheat/sorghum/SBM-based diets fed with or without microbial enzymes in diets on the performance, visceral organ development and digestibility of nutrients of broiler chickens. Four graded levels of CSM - none (0%), low (4%, 8%, and 12%), medium (5%, 10%, and 15%), and high (6%, 12%, and 18%) of complete diets in starter, grower and finisher, respectively were fed with or without 100 mg/kg of xylanase and β-glucanase blend. Eight isocaloric and isonitrogenous diets were formulated using least-cost method to meet the nutrient specifications of Ross 308 male broilers. Each treatment was randomly assigned to 6 replicates (10 birds per replicate). There were CSM-enzyme interactions (p < 0.05) on feed intake (FI) and weight gain (WG) in the starter phase. Enzyme supplementation improved (p < 0.05) feed conversion ratio (FCR) in the grower and finisher phases, and increased WG in growing and finishing birds. CSM inclusion reduced (p < 0.05) the weight of gizzard and proventriculus in starter chicks, while these organs were bigger (p < 0.05) in the grower phase. The test ingredient decreased (p < 0.05) small intestinal weight in starter and grower birds. The CSM increased the absolute weight of thighs (p < 0.05) while breast meat was increased (p < 0.01) by enzyme addition. Starch digestibility was improved (p < 0.01) by enzyme inclusion and decreased (p < 0.01) by CSM. Enzyme supplementation improved (p < 0.05) the ileal digestibility of gross energy and protein. The results demonstrate that CSM can substitute up to 90% SBM in broiler chicken diets without compromising performance, and the nutritive value of CSM-containing diets can effectively be improved by enzyme supplementation.