Vascular mitochondria constantly integrate signals from environment and respond accordingly to match vascular function to metabolic requirements of the organ tissues, while mitochondrial dysfunction contributes to vascular aging and pathologies such as atherosclerosis, stenosis, and hypertension. As an effective lifestyle intervention, exercise induces extensive mitochondrial adaptations through vascular mechanical stress and the increased production and release of reactive oxygen species and nitric oxide that activate multiple intracellular signaling pathways, among which peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) plays a critical role. PGC-1α coordinates mitochondrial quality control mechanisms to maintain a healthy mitochondrial pool and promote endothelial nitric oxide synthase activity in vasculature. The mitochondrial adaptations to exercise improve bioenergetics, balance redox status, protect endothelial cells against detrimental insults, increase vascular plasticity, and ameliorate aging-related vascular dysfunction, thus benefiting vascular health. This review highlights recent findings of mitochondria as a central hub integrating exercise-afforded vascular benefits and its underlying mechanisms. A better understanding of the mitochondrial adaptations to exercise will not only shed light on the mechanisms of exercise-induced cardiovascular protection, but may also provide new clues to mitochondria-oriented precise exercise prescriptions for cardiovascular health.