Brandão, L, de Salles Painelli, V, Lasevicius, T, Silva-Batista, C, Brendon, H, Schoenfeld, BJ, Aihara, AY, Cardoso, FN, de Almeida Peres, B, and Teixeira, EL. Varying the order of combinations of single- and multi-joint exercises differentially affects resistance training adaptations. J Strength Cond Res 34(5): 1254–1263, 2020—Our study aimed to compare the effects of multi-joint (MJ) and single-joint (SJ) exercises, either isolated or in combination, and in different orders, on cross-sectional area (CSA) of the pectoralis major (PM) and different heads of the triceps brachii (TB), as well as on the one-repetition maximum (1-RM) in the bench press and lying barbell triceps press. Forty-three young men were randomly assigned to one of 4 possible RT protocols: barbell bench press plus lying barbell triceps press (MJ + SJ, n = 12); lying barbell triceps press plus barbell bench press (SJ + MJ, n = 10); barbell bench press (MJ, n = 10); or lying barbell triceps press (SJ, n = 11). Results showed significant within-group increases in 1-RM bench press for MJ, MJ + SJ, and SJ + MJ but not for SJ. Conversely, significantly greater within-group increases in elbow extension 1-RM were noted for SJ, MJ + SJ, and SJ + MJ but not for MJ. Significantly greater increases in PM CSA were observed for MJ, MJ + SJ, and SJ + MJ compared with SJ. Significant increases in TB CSA were noted for SJ, MJ + SJ, and SJ + MJ, but not for MJ, without observed between-group differences. Individual analysis of TB heads showed significantly greater CSA increases in the lateral head for MJ, MJ + SJ, and SJ + MJ compared with SJ. Alternatively, significantly greater increases in the long head were observed for SJ, MJ + SJ, and SJ + MJ compared with MJ. CSA increases for the medial head were statistically similar between conditions. Our findings indicate that muscular adaptations are differentially affected by performance of MJ and SJ exercises.