The motion of the human knee during flexion and extension generates spatial movement. The current designs of many knee braces and prostheses fail to incorporate this complex motion. This paper presents a method for developing mechanisms with which to more accurately approximate the true movement of the human knee joint with an orthosis comprised of single degree of freedom (DoF) mechanisms. Digitized measurements of the relative motion of the tibia and femur were used to determine the design positions of the mechanisms. Analytical strategies were employed to synthesize suitable Stephenson six-bar linkages for the task of motion generation. The more desirable solutions were selected based on their ability to match the measured movement of the knee as well as the size of their operational envelope. Distinct, single DoF linkages were synthesized for the medial and lateral sides of the knee. Coordination, via attachment to the tibial portion of the orthosis, of these linkages provides a single DoF mechanism to approximate the complex motion of the tibia relative to the femur during flexion and extension.