Purpose. This study examined the sex-related differences in muscular performance and neuromuscular (electromyographic [EMG] and mechanomyographic [MMG] amplitude [AMP] and mean power frequency [MPF]) responses during fatiguing leg extension repetitions performed at the critical load (CL). Methods. Eleven men and nine women completed one-repetition maximum (1RM) testing, repetitions to failure at 50, 60, 70, and 80% 1RM to determine CL, and repetitions to failure at CL, on separate days. The EMG and MMG, AMP and MPF signals and number of repetitions completed were recorded. Results. There were no sex-dependent responses in the %1RM that corresponded to, the number of repetitions completed at, or the neuromuscular responses during repetitions performed to failure at CL. There were time-dependent responses in EMG AMP from 25-100% of total repetitions completed, respectively. The EMG MPF and MMG MPF demonstrated fatigue-induced decreases from 50-100% and at 100% of total repetitions completed, respectively. There was no change over time for MMG AMP. Conclusions. These findings indicated men and women responded similarly to leg extension exercise performed at the CL. Further, sex-dependent responses to fatiguing exercise may be related to the amount of active muscle mass engaged in exercise and the corresponding afferent feedback that influences peripheral fatigue and central drive during fatiguing tasks