Valgus bending and shearing of the knee have been identified as primary mechanisms of injuries in a lateral loading environment applicable to pedestrian-car collisions. Previous studies have reported on the structural response of the knee joint to pure valgus bending and lateral shearing, as well as the estimated injury thresholds for the knee bending angle and shear displacement based on experimental tests. However, epidemiological studies indicate that most knee injuries are due to the combined effects of bending and shear loading. Therefore, characterization of knee stiffness for combined loading and the associated injury tolerances is necessary for developing vehicle countermeasures to mitigate pedestrian injuries. Isolated knee joint specimens from postmortem human subjects were tested in valgus bending at a loading rate representative of a pedestrian-car impact. The effect of lateral shear force combined with the bending moment on the stiffness response and the injury tolerances of the knee was concurrently evaluated. In addition to the knee moment-angle response, the bending angle and shear displacement corresponding to the first instance of primary ligament failure were determined in each test. The failure displacements were subsequently used to estimate an injury threshold function based on a simplified analytical model of the knee. The validity of the determined injury threshold function was subsequently verified using a finite element model. Post-test necropsy of the knees indicated medial collateral ligament injury consistent with the clinical injuries observed in pedestrian victims. The moment-angle response in valgus bending was determined at quasistatic and dynamic loading rates and compared to previously published test data. The peak bending moment values scaled to an average adult male showed no significant change with variation in the superimposed shear load. An injury threshold function for the knee in terms of bending angle and shear displacement was determined by performing regression analysis on the experimental data. The threshold values of the bending angle and shear displacement estimated from the injury threshold function were in agreement with previously published knee injury threshold data. The continuous knee injury function expressed in terms of bending angle and shear displacement enabled injury prediction for combined loading conditions such as those observed in pedestrian-car collisions.