Obesity-related osteoarthritis (OA) is a complex, multifactorial condition that can cause significant impact on patients’ quality of life. Whilst chronic inflammation, adipocytokines and metabolic factors are considered to be important pathogenic factors in obesity related OA, there has been limited investigation into the biomechanical impact of obesity on OA development. This review aims to demonstrate that mechanical factors are the major pathological cause of obesity-related OA. The effect of obesity on pathological changes to the osteochondral unit and surrounding connective tissues in OA is summarized, as well as the impact of obesity-related excessive and abnormal joint loading, concomitant joint malalignment and muscle weakness. An integrated therapeutic strategy based on this multi-factorial presentation is presented, to assist in the management of obesity related OA. The translational potential of this article: Despite the high prevalence of obesity-related OA, there is no specific guideline available for obesity-related OA management. In this review, we demonstrated the pathological changes of obesity-related OA and summarized the impact of biomechanical factors by proposing a hypothetical model of obesity-related OA change. Therapeutic strategies based on adjusting abnormal mechanical effects are presented to assist in the management of obesity-related OA.