Trapeziometacarpal (TMC) osteoarthritis (OA) is a prevalent condition that significantly impacts hand function and quality of life. In this study we sought to close gaps in knowledge related to the initiation and progression of TMC OA on the tissue scale by evaluating the morphology and gross appearance, wear patterns, mechanical properties, subchondral bone morphology, and histological characteristics of the tissue across a spectrum of disease severity and by correlating each of these properties to the clinically assessed radiographic grade. Thirty-two cadaveric hand specimens were first assigned a radiographic grade by three hand surgeons. Trapezia were then evaluated for cartilage wear and eburnation. Cartilage mechanics were assessed via indentation testing across the TMC surface. Bone morphology was evaluated via micro-computed tomography, and stained histologic sections were assessed with histopathology scoring. Analysis revealed that radiographic grading is a lagging indicator of joint pathology, with degenerative changes occurring before radiographic evidence. While cartilage wear followed regional patterns (beginning at the volar and radial aspects), mechanical weakening of cartilage occurred uniformly across the joint. These findings suggest TMC OA involves both mechanical wear and biological factors, rather than being purely a “wear and tear” disease. We confirmed that radiographic staging is not sensitive to TMC OA initiation and early progression;​ however, it may still be useful for its predictive power in later stages of disease, given its strong correlations to both functional (cartilage mechanical properties) and structural (osteochondral histology score) outcomes. This understanding could inform the development of early interventions and more effective treatments.