Manual anatomical landmarking for morphometric knee bone characterization in orthopedics is highly time-consuming and shows high operator variability. Therefore, automation could be a substantial improvement for diagnostics and personalized treatments relying on landmark-based methods. Applications include implant sizing and planning, meniscal allograft sizing, and morphological risk factor assessment. For twenty MRI-based 3D bone and cartilage models, anatomical landmarks were manually applied by three experts, and morphometric measurements for 3D characterization of the distal femur and proximal tibia were calculated from all observations. One expert performed the landmark annotations three times. Intra- and inter-observer variations were assessed for landmark position and measurements. The mean of the three expert annotations served as the ground truth. Next, automated landmark annotation was performed by elastic deformation of a template shape, followed by landmark optimization at extreme positions (highest/lowest/most medial/lateral point). The results of our automated annotation method were compared with ground truth, and percentages of landmarks and measurements adhering to different tolerances were calculated. Reliability was evaluated by the intraclass correlation coefficient (ICC). For the manual annotations, the inter-observer absolute difference was 1.53 ± 1.22 mm (mean ± SD) for the landmark positions and 0.56 ± 0.55 mm (mean ± SD) for the morphometric measurements. Automated versus manual landmark extraction differed by an average of 2.05 mm. The automated measurements demonstrated an absolute difference of 0.78 ± 0.60 mm (mean ± SD) from their manual counterparts. Overall, 92% of the automated landmarks were within 4 mm of the expert mean position, and 95% of all morphometric measurements were within 2 mm of the expert mean measurements. The ICC (manual versus automated) for automated morphometric measurements was between 0.926 and 1. Manual annotations required on average 18 min of operator interaction time, while automated annotations only needed 7 min of operator-independent computing time. Considering the time consumption and variability among observers, there is a clear need for a more efficient, standardized, and operator-independent algorithm. Our automated method demonstrated excellent accuracy and reliability for landmark positioning and morphometric measurements. Above all, this automated method will lead to a faster, scalable, and operator-independent morphometric analysis of the knee.