Osteoarthritis (OA), a prevalent and debilitating condition, poses substantial diagnostic and therapeutic challenges. Our study leverages advanced quantitative MRI to construct a sophisticated 100-dimensional space mapping known risk factors, unveiling unique imaging biomarkers for early detection and causal analysis in OA incidence and knee replacement (KR) cohorts. This methodological innovation enables a data-driven exploration of OA pathophysiology. We identified distinctive imaging features that differentiate between individuals at risk of OA and controls, elucidating protective factors and risk enhancers. Specifically, our analysis revealed that variations in cartilage thickness and T2 relaxation times are associated with reduced OA risk, whereas alterations in the medial meniscus shape increase susceptibility. Additionally, we pinpointed biomarkers for KR candidates, including tibial bone shape and cartilage characteristics, with significant implications for understanding OA’s progression. Our findings provide a promising foundation for future research, tailored clinical trials, and personalized therapeutic approaches, marking a significant stride toward combating OA.