Sarcopenia is an age-related, systemic skeletal muscle disease that severely affects the health and quality of life of the elderly, serving as one of the leading causes of disability and increased social burden among this population. The imbalance between protein synthesis and degradation is a primary pathogenic mechanism, in which the ubiquitin-proteasome system (UPS), particularly E3 ubiquitin ligases (E3s), plays a crucial role in regulating muscle protein degradation. This article elucidates and summarizes the impact and mechanisms of E3s in sarcopenia-associated muscle atrophy, aiming to provide novel insights for basic research, the identification of therapeutic targets, and the development of preventive strategies for sarcopenia.