The relationship between muscle action and fatigue is not well understood, especially in terms of potential sex-specific differences. The purpose of this investigation was to determine whether a different number of repetitions could be performed on the individual muscle actions of the bench press and squat in men and women. Ten resistance-trained men (n = 10; age, 25.2 ± 1.2 years; height, 178.6 ± 8.8 cm; weight, 91.4 ± 18.1 kg; body fat, 12.7 ± 3.6%) and women (n = 10; age, 25.4 ± 2.4 years; height, 164 ± 4.0 cm; weight, 58.45 ± 3.3 kg; body fat, 20.8 ± 1.5%) participated in this balanced and randomized within-group study. Using 85% of a 1 repetition maximum, over the course of 3 visits, subjects performed 1 eccentric (ECC), concentric (CON), or combined (COMB) set to failure on the squat and bench press. Differences in muscle action and sex-specific number of repetitions to failure were compared on the squat and bench press, where significance was p ≤ 0.05. Across both exercises and sex, we observed significant differences between each of the 3 muscle actions, where the number of repetitions decreased from ECC to COMB to CON. While no sex-specific differences were observed in the squat, women performed significantly more repetitions on the ECC and CON muscle actions of the bench press. Men performed more combined repetitions, however, indicating a greater reliance on the stretch-shortening cycle. Different muscle actions contribute uniquely to the successful performance of a lift and fatigue. These contributions appear to differ in men and women.