Torsional profiles of the lower limbs, such as femoral anteversion, can dictate gait and mobility, joint biomechanics and pain, and functional impairment. It currently remains unclear how the interactions between femoral anteversion, kinematics, and muscle activity patterns contribute to joint biomechanics and thus conditions such as knee pain. This study presents a computational modeling approach to investigating the interactions between femoral anteversion, muscle forces, and knee joint loads. We employed an optimal control approach to produce actuator and muscle-driven simulations of the stance phase of gait for femoral anteversion angles ranging from −8° (retroversion) to 52° (anteversion) with a typically developing baseline of 12° of anteversion and implemented a Monte Carlo analysis for variations in lower limb muscle forces. While total patellofemoral joint load decreased with increasing femoral anteversion, patellofemoral joint load alignment worsened, and knee abduction/adduction magnitude increased with both positive and negative changes in femoral anteversion (p < 0.001). The rectus femoris muscle was found to greatly influence patellofemoral joint loads across all femoral anteversion alignments (R > 0.8, p < 0.001), and the medial gastrocnemius was found to greatly influence knee abduction/adduction moments for the extreme version cases (R > 0.74, p < 0.001). Along with the vastus lateralis, which decreased with increasing femoral anteversion (R = 0.89, p < 0.001), these muscles are prime candidates for future experimental and clinical efforts to address joint pain in individuals with extreme femoral version. These findings, along with future modeling efforts, could help clinicians better design treatment strategies for knee joint pain in populations with extreme femoral anteversion or retroversion.