Chronic stress and continually high glucocorticoid levels can induce muscle atrophy. Unfortunately, there is a lack of appropriate animal models for stress-induced muscle atrophy research. Corticotropin releasing factor-overexpressing (CRF-OE) mice are a transgenic model of chronic stress that exhibit increased plasma corticosterone levels and Cushing's syndrome; however, the skeletal muscle pathology of the CRF-OE mouse has not been well studied. We observed that male, 19-week-old CRF-OE mice had significantly lower skeletal muscle mass, average cross-sectional myofiber area, and total muscle protein content than their wild type (WT) littermates. Muscle function determined by grip strength, wire-hang, and open field tests showed that 19-week-old male CRF-OE mice had impaired physical ability. Additionally, the skeletal muscles of CRF-mice exhibited decreased expression of factors involved in the IGF-1/AKT/mTOR protein synthesis pathway and increased ubiquitin proteasome pathway activity compared to the WT control mice. In conclusion, 19-week-old CRF-OE mice display numerous features of muscle atrophy and thus serve as a model for investigating stress-induced muscle atrophy and interventions to target the deleterious effects of stress on skeletal muscle.