Sex differences in performance fatigability (PF) are task- and intensity-dependent, as variations in neuromuscular and vascular function modulate the ability to sustain torque output. However, few studies have examined differences in the onset of changes in neuromuscular and microvascular responses that contribute to declines in maximal torque production. Therefore, our purpose was to examine sex differences in PF, neuromuscular function, skeletal muscle tissue oxygenation (StO2), and torque during maximal dynamic muscle actions. Twenty-five recreationally active adults (n=13, males) performed 50 maximal isokinetic knee extensions with surface electromyographic amplitude (sEMG AMP) and near-infrared spectroscopy-derived StO2 recorded simultaneously from the dominant vastus lateralis. Seven mixed-factorial 2 (Sex: Males, females) × 10 (Time: Repetitions 1-5, 6-10, 11-15, 16-20, 21-25, 26-30, 31-35, 36-40, 41-45, 46-50) ANOVAs examined mean differences in torque, sEMG AMP, and StO2. PF was similar (p textgreater0.05) between sexes, yet males exhibited steeper and observable declines in torque at repetitions 21-25 (p = .014, d =0.994), whereas females exhibited a decline at repetitions 36-40 (p = .007, d =1.367). There was no significant interaction or main effects (p textgreater0.05) for sEMG AMP. The StO2 responses revealed a significant interaction (p textless.001, partial η2 = .705), indicating males exhibited more rapid declines and greater absolute decreases (15.3% ± 6.9 vs. 9.2% ± 4.9) in StO2 than females. These results suggest that males experience accelerated fatigue coinciding with greater impairments in muscle oxygenation. Future work should focus on developing strategies to overcome limitations in muscle oxygenation, thereby improving exercise tolerance and performance.