Objective The mechanism and severity of ankle cartilage degeneration caused by knee osteoarthritis remain unknown. It is proposed to establish two 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 and CAI on ipsilateral ankle cartilage degeneration. Method Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups which were induced to develop knee and ankle osteoarthritis, 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. Result A decline was observed in gait stability and balance of the surgical groups. Compared to the control group, a 23.20% increase in the time required to cross the balance beam and a 43.26% rise in the number of slips at 12 weeks postoperatively in the DMM group were found. Meanwhile, increases were also observed in ankle bone volume fraction and bone mineral density over time. These changes included wear and tear of the ankle cartilage, with the formation of osteophytes, and 88.89% increase in OARSI score. These changes in ankle joint were more pronounced in the CAI group. Conclusion A study of mouse model 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.