Background: Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Methods: Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Results: Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy1BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy1 BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. Conclusions: These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Clinical Relevance: Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise.