To examine the isolated and combined effects of sex and perceptual-motor function on single-leg squatting mechanics in males and females. We employed a cross-sectional design in a research laboratory. Fifty-eight females (22.2 ± 3.5 yrs, 1.60 ± .07 m, 64.1 ± 13.0 kg) and 35 males (23.5 ± 5.0 yrs, 1.80 ± .06m, 84.7 ± 15.3 kg) free from time-loss injury in the six months prior, vertigo, and vestibular conditions participated in this study. Independent variables were sex, perceptual-motor metrics (reaction time, efficiency index, conflict discrepancy), and interaction effects. Dependent variables were peak frontal plane angles of knee projection, ipsilateral trunk flexion, and contralateral pelvic drop during single-leg squatting. After accounting for the sex-specific variance and perceptual-motor function effects on frontal plane squatting kinematics, female sex amplified the associations of: higher reaction time, lower efficiency index, and higher conflict discrepancy with greater right ipsilateral peak trunk lean (R² = .13; p = .05); higher reaction time, lower efficiency index, and higher conflict discrepancy with decreased right contralateral pelvic drop (R² = .22; p < .001); higher reaction time and lower conflict discrepancy with greater right frontal plane knee projection angle (R² = .12; p = .03); and higher reaction time with greater left frontal plane knee projection angle (R² = .22; p < .001). Female sex amplified the relationship between perceptual-motor function and two-dimensional frontal plane squatting kinematics. Future work should determine the extent to which perceptual-motor improvements translate to safer movement strategies.

• Sex moderated the relationship between perceptual-motor function and biomechanics, such that females with slower reaction times displayed more medially-projected knees, while males with slower reaction times exhibited altered frontal plane pelvic motion.

• Clinically feasible choice reaction time measures can be used as gross indicators of one’s propensity for altered single-leg squatting mechanics.

• Future work should investigate the extent to which these relationships can be modified in each sex.