The purpose of this study was to determine the effect of impaired quadriceps function on knee joint biomechanics and neuromuscular function during gait. Surface electromyograms, three-dimensional motion and ground reaction forces were collected during gait before and after 20 healthy adults completed a high intensity quadriceps fatigue protocol. Pattern recognition techniques were utilized to examine changes in amplitude and temporal characteristics of all gait variables. The fatigue protocol resulted in decreased knee extensor torque generation and quadriceps median power frequencies for 18 of 20 participants (p < 0.05). The gait data from these 18 participants was analyzed. The knee external rotation angle increased (p < 0.05), the net external flexion and external rotation moments decreased (p < 0.05), and the net external adduction moment increased (p < 0.05). Post-fatigue changes in periarticular muscle activation patterns were consistent with the biomechanical changes, but were not significantly altered. Even for this low demand task of walking the knee motion and loading characteristics were altered following a high intensity fatigue protocol in a manner that may place the knee joint at greater risk for joint pathology and injury.