This study investigated whether the sex difference in fatigability of the knee extensors (KE) is explained by the sex difference in fatigue-induced changes in the shear modulus of one or more muscles of KE in 18 young men and 23 young women. The shear moduli of the resting rectus femoris and medial and lateral vastus muscles (VL) were measured before and after a sustained contraction at 20% peak torque during a maximal voluntary isometric contraction of KE until the endurance limit, in addition to evoked torque and voluntary activation (VA%). The fatigue-induced decrease in maximal muscle strength was more prominent in men than in women. Only the VL shear modulus for men increased after the fatiguing task, and a sex difference was observed in the percentage change in the VL shear modulus before and after the fatiguing task. The fatigue-induced decreased ratio was greater for men than for women in evoked torque, but not in VA%. These results suggest that although peripheral and central fatigue both influenced the fatigue-induced decrease in maximal muscle strength regardless of sex, the sex difference in KE fatigability is explained by that in peripheral fatigue, particularly the degree of peripheral VL fatigue.