Seedlings of 462 sorghum lines were screened to identify resistance to the sugarcane aphid, Melanaphis sacchari (Zehntner). About 7% of the lines exhibited resistance in the seedling stage in greenhouse trials. In an advanced screening experiment, 12 sorghum lines had resistance ratings of 1.0–3.0 (highly resistant or resistant). In a similar test, older and larger plants of the same lines were as resistant as in the seedling stage. Lines IS12664C, IS12609C, IS12158C, and IS12661C were highly resistant in preliminary and advanced screening trials. Antixenosis was shown to be a mechanism of resistance. Sorghum lines IS12664C, IS1144C, IS1598C, and IS12661C were less preferred than ‘Mtode’, a susceptible sorghum. Based on greenhouse and field trials, antibiosis adversely affected aphid longevity, days reproducing, and progeny production. On the least antibiotic sorghums, longevity, days reproducing, and number of nymphs produced were as high as 13.7, 6.0, and 26.6, respectively. On the most antibiotic sorghums, these values were 4.5, 0.0, and 0.0. Resistance appeared to be controlled by a dominant gene, but there were indications of modifiers linked to major genes.