The objective of the study was to evaluate the response of non-preference and severity of damage by Melanaphis sacchari (Zehntner) in commercial cultivars of sorghum (Sorghum bicolor (L.) Moench). Effect of antixenosis and enzymatic activity were evaluated in 11 sorghum cultivars with a completely randomized design with 10 replications in a laboratory. In the field, damage severity was evaluated in 10 genotypes with a randomized complete block design with three replications. M. sacchari feeding and reproducing in a laboratory showed less preference for DKS 26, DKS 2805, GW 9320, and GW 1160, which suggested a high level of antixenosis by the genotypes. Genotype DKS 2805 had the most peroxidase activity, suggesting the genotype increased peroxidase activity to resist feeding by M. sacchari. In the field, DKS 2805 and GW 9320 were resistant and moderately resistant to the pest. Resistance of DKS 2805 might be caused by antixenosis and high peroxidase activity, while GW 9320 might be by antixenosis alone. Resistant genotypes DKS 2805 and GW 9320 should be part of an integrated management program against M. sacchari.