The ability of mitochondria to remodel through fission and fusion is critical to health and disease. In skeletal muscle, efficient and effective mitochondrial dynamics are required to maintain exercise capacity, substrate utilization, and glucose homeostasis, and their disruption results in metabolic disease. The cytoskeleton has emerged as a key regulator of mitochondria dynamics, but our knowledge of the cytoskeletal factors and mechanisms mediating these processes in skeletal muscle is largely incomplete. Ankyrins and spectrins are ubiquitously expressed, cytoskeleton-associated, sub-membrane scaffolding proteins whose canonical roles are to organize membrane-associated ion channels and cell adhesion molecules, often in a hierarchical and cooperative manner. Variants in ankyin-B (AnkB), encoded by ANK2, increase risk for cardio-metabolic diseases in humans and cause age- or diet-dependent metabolic syndrome in mice. Variants in beta (β)II- spectrin, encoded by SPTBN1, result in a neurodevelopmental disorder comorbid with muscle weakness and loss of muscle tone. However, the metabolic roles of AnkB and in βII- spectrin in skeletal muscle have not been characterized. Here, we leverage the constitutive and specific muscle knock-out of either AnkB (SKM-AnkB-KO) or βII- spectrin (SKM- βIIS-KO) to assess the muscle-autonomous roles of these proteins. We find that both SKM-AnkB-KO and SKM- βIIS-KO mice have reduced endurance exercise capacity, independently of mitochondrial mass. In SKM-AnkB-KO mice, exercise deficits are accompanied by reductions in fatty acid oxidation, a hyperfused mitochondrial network, altered levels and recruitment of key components of mitochondrial fission machinery, and impaired mitophagy in response to exercise. We also demonstrate that AnkB directly binds mitochondrial fission effectors in muscle, and its exogenous expression in AnkB-KO myoblasts rescues mitochondrial morphology. In SKM- βIIS-KO mice, exercise deficits are accompanied by increased body weight and reduced abundance of key fission effector molecules in mitochondria-rich muscle, in addition to hyperpolarization of the mitochondrial network and disruptions in cristae ultrastructure. Together, these data support a role of AnkB, and potentially βII-spectrin, in remodeling the mitochondrial network, which is critical to maintain exercise capacity and metabolic homeostasis.