Neuromuscular fatigue exacerbates abnormal landing strategies, which may increase noncontact anterior cruciate ligament (ACL) injury risk. The synergistic actions of quadriceps and hamstrings (QH) muscles are central to an upright landing posture, though the precise effect of simultaneous fatigue of these muscles on landing and ACL injury risk is unclear. Elucidating neuromechanical responses to QH fatigue thus appears important in developing more targeted fatigue-resistance intervention strategies. The current study thus aimed to examine the effects of QH fatigue on lower extremity neuromechanics during dynamic activity. Twenty-five healthy male and female volunteers performed three single-leg forward hops onto a force platform before and after QH fatigue. Fatigue was induced through sets of alternating QH concentric contractions, on an isokinetic dynamometer, until the first five repetitions of a set were performed at least 50% below QH peak torque. Three-dimensional hip and knee kinematics and normalized (body mass x height) kinetic variables were quantified for pre- and postfatigue landings and subsequently analyzed by way of repeated- measures mixed-model ANOVAs. QH fatigue produced significant increases in initial contact (IC) hip internal rotation and knee extension and external rotation angles (p < .05), with the increases in knee extension and external rotation being maintained at the time of peak vertical ground reaction force (vGRF) (p < .05). Larger knee extension and smaller knee flexion and external rotation moments were also evident at peak vGRF following fatigue (p < .05). Females landed with greater hip flexion and less abduction than males at both IC and peak vGRF as well as greater knee flexion at peak vGRF (p < .05). The peak vGRF was larger for females than males (p < .05). No sex x fatigue effects were found (p > .05). Fatigue of the QH muscles altered hip and knee neuromechanics, which may increase the risk of ACL injury. Prevention programs should incorporate methods aimed at countering QH fatigue.