The purpose of this study was to evaluate the effects of the replacement of whole-plant corn silage (WPCS) by whole-plant sesame silage (WPSS) in diets of lambs on leg tissue composition, physicochemical properties, and fatty acids profile of the meat. Forty castrated Santa Ine<SIC>s crossbred lambs presenting an average initial body weight (iBW) of 21.8 +/- 1.97 kg were distributed in a randomized block design with four treatments [four replacement levels: (control (no sesame), 333, 670, and 1000 g/kg of DM)] in ten replications. No effect (P > 0.05) of replacing WPCS with WPSS was observed on DM intake, final weight at slaughter, weight gain, leg weight, the proportion of muscle (M), bone (B), fat (F), and other tissues, muscularity, M:B ratio, M:F ratio, protein content, ash, pH, water holding capacity, cooking losses, shear force, color parameters (L*, a*, b*, C* and H*), EPUFA, EMUFA:ESFA ratio, En-6:En-3 ratio, h:H, atherogenicity index (AI) and on the activity of enzymes Delta 9-desaturase C18 and elongase. WPSS promoted quadratic increase (P < 0.05) in the moisture content and quadratic increase trend in C4:0 (P = 0.08). The inclusion of WPSS caused linear increases (P < 0.05) in the concentrations of C18:1 n-11trans, C18:2 c9trans-11 (CLA), EMUFAtrans, and EPUFA:ESFA ratio, and linear increase trend in C18:2 trans10c12 (P = 0.06) and C18:3 n-3 (P = 0.08). It was observed a linear decrease (P < 0.05) in the contents of C16:0, total FA, ESFA, EMUFA, EMUFAcis, and desirable FA, and a linearly decreasing trend in the thrombogenicity index (TI; P = 0.07). En-6 presented quadratic reduction (P = 0.03), while En-3 (P = 0.07) and Delta 9-desaturase C16 enzyme activity (P = 0.06) tended toward quadratic reduction. WPSS can fully replace WPCS as it does not compromise performance, tissue composition, and meat physico-chemical parameters, and improves the quality of meat fat as it reduces ESFA and TI and increases CLA content and PUFA:SFA ratio.