Osteoarthritis (OA) is the most common chronic degenerative joint disease in clinical practice. Its core characteristics include progressive degradation of articular cartilage, abnormal remodeling of subchondral bone, and synovial inflammation; to date, there remains no curative treatment. Autophagy, as a core degradation mechanism for maintaining intracellular homeostasis, plays a crucial role in the pathogenesis and progression of OA due to its functional dysregulation. It exhibits dynamic, phasic, and bidirectional regulatory characteristics throughout the OA process, and abnormalities in its activity directly affect the survival status of chondrocytes. This article systematically reviewed the multilevel interactive regulatory network of autophagy in OA, focusing on the mTOR-centered signaling pathway, key molecular nodes such as forkhead box O (FoxO)/silent mating type information regulation 2 homolog (SIRT)/hypoxia inducible factor (HIF), as well as the epigenetic regulatory roles of non-coding RNAs and exosome-mediated intercellular communication mechanisms, thereby providing a systematic theoretical basis for precision-targeted autophagy-based therapies for OA.