Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (μCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments; however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.