Anterior cruciate ligament (ACL) injuries occur in over 200,000 individuals per year in the United States. Quadriceps central activation failure (CAF) is a common consequence of these knee injuries, though why it presents remains elusive. Neuromuscular impairments resulting from ACL injury may not be limited to the muscles crossing the knee joint, however, though limited data are available to confirm this. The overall goal of this dissertation is to examine the muscle dysfunction associated with ACL injury and reconstruction, possible mechanisms leading to the lingering quadriceps muscle weakness after ACL reconstruction (ACLr), and to determine the immediate impacts of this weakness on the affected individual. In the first study, I sought to establish the presence of muscle dysfunction throughout the lower extremity following ACL injury and ACLr. I found that significant quadriceps and hamstrings strength deficits were present in the injured/reconstructed limb compared to the contralateral side both pre- and post-operatively, with pre-operative injured limb strength deficits also present compared to healthy individuals. There was no hip or ankle weakness, however, compared to healthy individuals. Given the presence of quadriceps weakness following ACLr, identifying the contributing factors to this muscle weakness seemed critical. Therefore, in study two I examined the contributions of quadriceps atrophy and CAF to persistent quadriceps strength impairments. Individuals who were six-months post-operatively following ACLr underwent quadriceps CAF and magnetic resonance imaging assessment. Results demonstrated that neither quadriceps CAF nor atrophy significantly contributed to the persistent quadriceps weakness in these individuals. Finally, I examined the effects of neuromuscular fatigue on quadriceps strength, CAF, and lower extremity biomechanics after ACLr. Individuals 7–10 months after ACLr demonstrated lower extremity biomechanics consistent with non-contact ACL injury risk prior to fatigue. Both ACLr and healthy individuals demonstrated greater quadriceps weakness and CAF following fatigue. Healthy individuals concurrently altered their biomechanics, potentially increasing their non-contact ACL injury risk. Surprisingly, ACLr subjects demonstrated similar, potentially injurious sagittal plane biomechanics pre- and post-fatigue, suggesting that reconstruction and/or rehabilitation are not sufficiently reducing the biomechanical risk factors for re-injury when individuals return to activity.