Objective To establish two osteoarthritis models of destabilization of the medial meniscus (DMM) and chronic ankle instability (CAI) in mice, and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration. Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups (DMM group and CAI group), respectively. The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation, imaging techniques and histopathology analysis in each group of mice over a 12-week period. Results A decline in gait stability and balance was observed in two surgical groups. Compared to the control group, the time required to cross the balance beam was increased by 23.20%, and the number of slips was increased 43.26% at 12th week postoperatively in the DMM group. The bone volume fraction and bone mineral density of ankle joints also increased. Meanwhile, wear and tear of the ankle cartilage were found, with the formation of osteophytes, and OARSI score was increased by 88.89%. These changes in ankle joint were more pronounced in the CAI group. Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion. Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration, while the damage was less severe than that observed in CAI.