Morphological changes in knee cartilage subregions are valuable imaging-based biomarkers for understanding progression of osteoarthritis, and they are typically detected from magnetic resonance imaging (MRI). So far, accurate segmentation of cartilage has been done manually. Deep learning approaches show high promise in automating the task;​ however, they lack clinically relevant evaluation. We introduce a fully automatic method for segmentation and subregional assessment of articular cartilage, and evaluate its predictive power in context of radiographic osteoarthritis progression. Two data sets of 3D double-echo steady-state (DESS) MRI derived from the Osteoarthritis Initiative were used:​ first, n = 88;​ second, n = 600, 0-/12-/24-month visits. Our method performed deep learning-based segmentation of knee cartilage tissues, their subregional division via multi-atlas registration, and extraction of subregional volume and thickness. The segmentation model was developed and assessed on the first data set. Subsequently, on the second data set, the morphological measurements from our and the prior methods were analyzed in correlation and agreement, and, eventually, by their discriminative power of radiographic osteoarthritis progression over 12 and 24 months, retrospectively. The segmentation model showed very high correlation (r > 0.934) and agreement (mean difference < 116 mm³) in volumetric measurements with the reference segmentations. Comparison of our and manual segmentation methods yielded r = 0.845–0.973 and mean differences = 262–501 mm³ for weight-bearing cartilage volume, and r = 0.770–0.962 and mean differences = 0.513–1.138 mm for subregional cartilage thickness. With regard to osteoarthritis progression, our method found most of the significant associations identified using the manual segmentation method, for both 12- and 24-month subregional cartilage changes. The method may be effectively applied in osteoarthritis progression studies to extract cartilage-related imaging biomarkers.