With the transition of China's animal husbandry towards intensification, investigating physiological regulatory mechanisms at the cellular level is of great significance for ensuring animal health and improving production efficiency. As a key intracellular energy sensor, AMP−activated protein kinase (AMPK) plays a multidimensional regulatory role in the process of mitophagy to maintain cellular homeostasis. AMPK can not only directly regulate mitophagy but also influence it through downstream signaling pathways such as ULK1, PGC−1α, and mTOR. This review systematically summarizes the molecular mechanisms by which AMPK mediates mitophagy and its role in animal physiological health. It elaborates on the structure, function, and activation mechanisms of AMPK, as well as its regulation of mitophagy through both direct (e.g., phosphorylating MFF, activating TBK1) and indirect pathways (modulating ULK1, PGC−1α, and mTOR signaling). The synergistic protective effects of AMPK and mitophagy under conditions such as nutrient deficiency, oxidative stress, and disease infection are analyzed. Furthermore, the positive impacts of this regulatory axis on animal muscle development, meat quality, antioxidant capacity, and immune function are discussed. The aim is to provide a scientific theoretical basis for promoting healthy animal growth through the exploration of physiological regulatory mechanisms..