Injuries to the knee are among the most common injuries in sports. A frequent and serious sports injury is that of an anterior cruciate ligament (ACL) rupture in the knee. Injury mechanisms have been documented from sports medicine patients suffering noncontact ACL tears. A hypothesis of the study was that the external tibial and valgus femoral rotations frequently identified after ACL injury are not representative of the relative displacements that cause isolated ACL failure to occur. The ACL is the primary restraint for anterior tibial subluxation, a co-primary restraint for internal tibial rotation and hyperextension, and a secondary restraint for valgus bending. A second hypothesis of this study was that tibiofemoral compression will produce anterior tibial subluxation and isolated ACL injuries, while other loading mechanisms will produce combination ligament injuries. Lower extremity joint injury is often accompanied by undiagnosed cartilage or bone damage in the form of fissures or “bone bruises”, respectively. Posttraumatic osteoarthritis has been demonstrated to occur at a high incidence rate following ACL injury. This disease may be initiated by the acute compressive trauma that occurs at the moment of ligamentous injury. A final hypothesis of the study was that the mechanism-based clinical classification of knee injuries and bone bruise patterns would correspond to characteristic distributions of high levels of contact pressure and osteochondral microdamage across the tibial plateau for each loading mechanism. The four specific loading mechanisms investigated here were;​ tibiofemoral compression, internal tibial torsion, hyperextention and valgus bending. This dissertation combines human cadaver studies with a computational model to validate the bone bruise “footprint” patterns associated with each injury mechanism. The peak forces/moments, relative knee joint displacements/rotations and type of failure were documented. Isolated ACL injuries occur from tibiofemoral compression, but internal tibial torsion and valgus bending caused combined medial collateral ligament injury. Hyperextension caused combined posterior and anterior cruciate ligament injuries. Tibiofemoral compression produced anterior tibial subluxation leading up to ACL injury. After failure, there were significant increases in external tibial rotation and valgus knee bending. Therefore, the vertical ground reaction force and muscle contraction that produces tibiofemoral compression should be considered as an important loading mechanism for studies of sports ACL injury scenarios. In addition, each loading mechanism produced distinct contact pressure distributions which correlated well with the location of osteochondral microdamage. The tibiofemoral compression, hyperextension and valgus bending loading mechanisms produced regions of contact pressure exceeding 30 MPa. In the computational model, this contact pressure produced maximum shear stresses in the articular cartilage, subchondral bone and trabecular bone which exceeded the threshold for predicted tissue damage. Therefore, even if knee joint motion is constrained and the ligamentous injuries are prevented, there is a long term risk of developing post-traumatic osteoarthritis from these levels of knee loading. The data presented in this dissertation may be applicable to injury prediction/prevention, and for clinicians to help diagnose injuries associated with ACL trauma.