Clinical studies including thousands of magnetic resonance imaging (MRI) scans offer potential for pathogenesis research in osteoarthritis. However, comprehensive quantification of all bone, cartilage, and meniscus compartments is challenging. We propose a segmentation framework for fully automatic segmentation of knee MRI. The framework combines multiatlas rigid registration with voxel classification and was trained on manual segmentations with varying configurations of bones, cartilages, and menisci. The validation included high- and low-field knee MRI cohorts from the Center for Clinical and Basic Research, the osteoarthritis initiative (QAI), and the segmentation of knee images10 (SKI10) challenge. In total, 1907 knee MRIs were segmented during the evaluation. No segmentations were excluded. Our resulting OAI cartilage volume scores are available upon request. The precision and accuracy performances matched manual reader re-segmentation well. The cartilage volume scan-rescan precision was 4.9% (RMS CV). The Dice volume overlaps in the medial/lateral tibial/femoral cartilage compartments were 0.80 to 0.87. The correlations with volumes from independent methods were between 0.90 and 0.96 on the OAI scans. Thus, the framework demonstrated precision and accuracy comparable to manual segmentations. Finally, our method placed second for cartilage segmentation in the SKI10 challenge. The comprehensive validation suggested that automatic segmentation is appropriate for cohorts with thousands of scans.