This study evaluates knee joint loading during gait and step-up-and-over tasks in control subjects, subjects with early knee OA and those with established knee OA. Thirty-seven subjects with varying degrees of medial compartment knee OA severity (eighteen with early OA and sixteen with established OA), and nineteen healthy controls performed gait and step-up-and-over tasks. Knee joint moments, contact forces (KCF), the magnitude of contact pressures and center of pressure (CoP) location were analyzed for the three groups for both activities using a multi-body knee model with articular cartilage contact, 14 ligaments, and six degrees of freedom tibiofemoral and patellofemoral joints. During gait, the first peak of the medial KCF was significantly higher for patients with early knee OA (p = 0.048) and established knee OA (p = 0.001) compared to control subjects. Furthermore, the medial contact pressure magnitudes and CoP location were significantly different in both groups of patients compared to controls. Knee rotation moments (KRMs) and external rotation angles were significantly higher during early stance in both patient groups (p < 0.0001) compared to controls. During step-up-and-over, there was a high variability between the participants and no significant differences in KCF were observed between the groups. Knee joint loading and kinematics were found to be altered in patients with early knee OA only during gait. This is an indication that an excessive medial KCF and altered loading location, observed in these patients, is a contributor to early progression of knee OA.