Musculoskeletal models of the lower limb lend insight into muscle forces and joint mechanics during dynamic activities. However, traditional musculoskeletal modeling is based on rigid body assumptions, and frequently represents the knee as a hinge joint, neglecting the complex interactions between the patella, femur, and tibia. Implementation of the musculoskeletal modeling framework in an explicit finite element environment allows joint contact to be easily incorporated, as well as representation of any structure as rigid or fully deformable in order to evaluate, for example, implant stresses or bone strain. Prediction of these values is particularly valuable when evaluating implant mechanics after total knee replacement. A finite element, musculoskeletal model of an implanted right lower limb was constructed, including thirteen muscles crossing the knee joint. A Hill-type muscle model was developed to allow muscle activation within the explicit FE framework. Muscle forces were predicted by optimization of muscle activation patterns during flexion-extension and chair-rise activities. The effect of muscle path representation was investigated using two approaches: lines of action directly between the origin and insertion sites of the muscles, and lines of action along the centroid of the muscle bodies. Incorporating anatomic muscle paths into the model reduced the predicted peak quadriceps force during the chair-rise activity by 46%, and reduced the peak tibio-femoral contact pressure by 14%. In addition, bone strain was predicted during the activity for the implanted patella, and showed peak bone strain at the edge of the implant near the inferior pole. The muscle-activated models demonstrated the advantages of an explicit finite element framework, and allow rapid, rigid body simulation in addition to the full contact, deformable analyses when greater resolution is required.