Extant mammals are ecologically diverse, having evolved a remarkable array of locomotor ecologies. Evolution of the therian-type forelimb was a key innovation, and musculoskeletal reorganization of the forelimb in therians is also associated with the acquisition of upright posture. Despite a rich fossil record, disagreement persists over when major functional changes in forelimb use and posture occurred during the evolution of mammals, exacerbated by lack of data from extant analogues. To investigate the functional impacts of forelimb reorganization in therians, we created digital musculoskeletal models of three extant taxa which span the sprawling-erect transition; Salvator merianae, a sprawling reptile; Tachyglossus aculeatus a sprawling monotreme mammal; and Didelphis virginiana, an upright therian mammal. From the musculoskeletal models we estimated and compared osteological range of motion (ROM) as well as muscle moment arms (MMA) at the shoulder joint. Based on published in vivo data, we predicted that ROM and MMA would be highest for forelimb long-axis rotation in sprawling taxa, and for flexion in upright taxa. The upright Didelphis did have the highest MMA for forelimb flexion, but our other predictions regarding long-axis rotation were not met; the sprawling taxa, Tachyglossus and Salvator, were better characterized by greater abduction MMA and high abduction-adduction ROM. Our data reveal a complex overall pattern, with each taxon showing a unique combination of biomechanical traits. We suggest that the sprawling-erect transition in the mammalian lineage was likely not straightforward, and there is important biomechanical variation within each of these broad locomotor categories.