Abstract In this work, a friction and wear simulator was used to reproduce the Anterior-Posterior (AP) sliding and the Flexion-Extension (FE) rotation generated in the knee joint during human gait cycle. We chose to simplify the contact geometry between the Total Knee Arthroplasty (TKA) femoral component and tibial insert. A 304L stainless steel cylinder which replaces the femoral component was loaded onto a flat High Density Polyethylene (HDPE) block which replaces the tibial insert. The tribological behavior of the considered contact was analyzed by tracking the number of cycles, the friction coefficient, the roughness of the wear track on HDPE, the HDPE weight loss and the damage mechanisms. The friction coefficient shows a gradual increase with the number of cycles for both AP and FE kinematics. The evolution of friction coefficient with the number of cycles is not affected by the value of the imposed normal load in the case of AP sliding. For the FE rotation, decreased friction coefficient is obtained when the imposed normal load increases. For both considered AP and FE kinematics, the roughness of the wear track on the HDPE is not affected by the imposed normal load. It shows a progressive decrease when the number of cycles increases. The wear of HDPE obeys the Archard law and the wear coefficient increases with the normal force. For a given value of normal load, the obtained wear coefficient for the AP sliding is larger than that obtained for FE rotation. A predominant adhesive wear mechanism was identified for both AP and FE kinematics. Under the same normal load, damage development in terms of plastic deformation, micro-cracking and debonding is more pronounced for the AP sliding if compared with the FE rotation. For a given kinematics, the damage severity increases with the normal load. This finding is in good agreement with the predicted values of the wear coefficient according to the Archard law.