Smut is a major disease of sugarcane plants and is caused by the fungus Ustilago scitaminea. Resistance to smut seems to be a multifactorial process. The current criteria for the selection of resistant varieties are applied by discarding sensitive specimens rather than improving resistance mechanisms through analysis of the molecular bases for resistance. This paper correlates the sensitivity or resistance to smut with changes in sugarcane leaf levels of free phenolic compounds, and phenylalanine ammonia-lyase and peroxidase activities, in response to elicitors from U. scitaminea mycelium. The interaction was studied in sugarcane leaf discs obtained from cultivars Barbados 42231, which is susceptible to smut, and Mayarí 55–14, which is highly resistant to smut. The elicitors enhanced the levels of hydroxycinnamic and hydroxybenzoic acids mainly in the resistant cultivar. p-Coumaric (from hydroxycinnamic acids) and syringic acid (from hydroxybenzoic acids) were the phenolic acids that showed a major accumulation pattern. Cultivar Mayarí 55–14 had high phenylalanine ammonia-lyase activity without accumulation of free hydroxycinnamic acids. The increase in peroxidase activity was important in the defence mechanism but was not a determinant for the defence. Cultivar Barbados 42231 showed low phenylalanine ammonia-lyase activity as accumulation of caffeic acid produced feedback inhibition of the enzyme. A simple model for studying the level of resistance of new sugarcane clones for helping breeding programs is proposed.