Mechanisms of femoral fracture of the condyles and shaft were experimentally investigated through controlled knee impact of denuded femurs in six human cadavers. High-speed movies recorded knee joint compression, femoral displacements and deformation, and fracture initiation. Fracture initiated at 10.6 ± 2.7 kN knee load after 1.3 ± 0.1 cm of knee joint compression for a 10.1 kg rigid impact at 13.2 ± 1.4 m/s. Interestingly, fracture occurred 0.5 ms–1.5 ms after the peak in applied knee load of 18.3 ± 6.9 kN, probably because a significant portion of the load is developed by inertial accelerations displacing the femur and coupled masses. Axial strain measurements at the femoral midshaft showed increasing anteroposterior bending and compressional deformations until the initiation of observed fracture. The kinematics of the observed fracture and the midshaft deformational strains indicate that fracture is predominantly due to tensile strain from anteroposterior bending of the femoral shaft or patellar wedging of the condyles.