Obesity is a well-defined mechanical factor for osteoarthritis (OA). More than one-third of adults in the United States are obese, and one in three obese adults has arthritis. In obese individuals, knee pain is highly prevalent and is often thought to be the first symptom of knee OA. In the pathomechanics of knee OA, altered kinematics and contact location in the knee joint are potent contributors to OA initiation and progression. However, such kinematics and cartilage contact location in obese individuals, and how the knee joint responses to excess load due to obesity are not clear and understudied, mainly limited by the instrumentations. Therefore, we conducted a series of dissertation studies to investigate the effect of weight on the knee joint kinematics in six degrees of freedom (6DOF) and cartilage contact location using a fluoroscopic imaging system with magnetic resonance-based morphological models. In Study 1, the 6DOF kinematic analysis showed that obese individuals with knee pain walked with a reduced range of flexion-extension motion and a reduced medial-lateral translation compared with nonobese controls. In Study 2, the cartilage contact analysis showed that obese individuals experienced different contact location on both the tibial and femoral cartilage surfaces during walking when compared with a healthy group, while pain had a minimal effect on the cartilage contact location. In Study 3, we followed up with the obese individuals in Study 1 and the kinematic analysis showed that the change in range of the flexionextension and adduction-abduction motion during gait were associated with the change in body weight;​ however, knee pain was not associated with the kinematic change. In conclusion, this series of dissertation studies suggests that the kinematics of the knee in obese individuals with knee pain was modifiable through weight loss. Weight management should be addressed more than controlling for pain in obese individuals with pain, as pain management might not able to restore the contact locations.