In the United States, an estimated 100,000 anterior cruciate ligament (ACL) injuries occur every year. Despite decades of research, to this date, the mechanism or mechanisms of non-contact ACL injuries are not well understood. This is primarily because trials cannot be conducted on live subjects to understand the injury mechanism, and it is difficult to instrument a live human knee to measure the response of tissues during dynamic activities. In this paper, we present a dynamic knee injury simulator capable of in-vitro modeling of the ACL injury during jump-landing activity. This system was used to simulate jump-landing on cadaveric knees and to successfully test which conditions would result in isolated ACL injury. A restricted flexion of the hip (a hip that flexes minimally or not at all during landing), combined with low quadriceps and hamstring force levels during landing were found to be conducive to ACL injury. Elevated levels of quadriceps force prevented the injury from occurring even under restricted hip flexion conditions. The measured strain rates in the ACL tissue during injury causing activities were over 250%/s.