Objective.This study examined sex-related differences in fatigability and neuromuscular responses using surface electromyographic (sEMG) and mechanomyographic (sMMG) amplitude (AMP) and frequency (MPF) during fatiguing, maximal, bilateral isometric leg extensions.Approach.Twenty recreationally active males and females with resistance training experience performed continuous, maximal effort, bilateral isometric leg extensions until their force reduced by 50%. Linear mixed effect models analyzed patterns of force, sEMG, and sMMG AMP and MPF responses in the dominant limb. An independent samples t-test compared time-to-task failure (TTF) between sexes.Main Results.There were no significant differences in TTF between males and females. However, males experienced a greater rate of force loss compared to females. Furthermore, sEMG AMP and MPF and sMMG AMP responses followed similar linear trends for both sexes, while sMMG MPF showed non-linear responses with sex-dependent differences.Significance.These data suggest that although TTF was similar, males had a higher rate of force reduction, likely due to greater absolute strength. Furthermore, despite parallel changes in sEMG AMP and MPF, as well as sMMG AMP, the divergent responses observed in sMMG MPF highlight sex-dependent differences in how males and females experience changes in the firing rates of active motor units during sustained maximal contractions.