Anterior cruciate ligament (ACL) injuries commonly occur during single-leg landing tasks and are a burdensome condition. Previous studies indicate that muscle forces play an important role in controlling ligamentous loading, yet these studies have typically used cadaveric models considering only the knee-spanning quadriceps, hamstrings, and gastrocnemius muscle groups. Any muscles (including non-knee-spanning muscles) capable of opposing the anterior shear joint reaction force and the valgus joint reaction moment are thought to have the greatest potential for protecting the ACL from injury. Thus, the purpose of this study was to investigate how lower-limb muscles modulate knee joint loading during a single-leg drop landing task. An electromyography-informed neuromusculoskeletal modeling approach was used to compute lower-limb muscle force contributions to the anterior shear joint reaction force and the valgus joint reaction moment at the knee during a single-leg drop landing task. The average shear joint reaction force ranged from 153 N of anterior shear force to 744 N of posterior shear force. The muscles that generated the greatest posterior shear force were the soleus, medial hamstrings, and biceps femoris, contributing up to 393 N, 359 N, and 162 N, respectively. The average frontal plane joint reaction moment ranged from a 19 Nm varus moment to a 6 Nm valgus moment. The valgus moment was primarily opposed by the gluteus medius, gluteus minimus, and soleus, with these muscles providing contributions of up to 38, 22, and 20 Nm toward a varus moment, respectively. The findings identify key muscles that mitigate loads on the ACL.