Infected bone defects (e.g., osteomyelitis) present a complex clinical challenge characterized by persistent biofilms, intracellular pathogens, and compromised bone regeneration. We hypothesized that a bioadaptive magnesium implant with sequential coating/substrate degradation could render staged anti-infective and pro-regenerative therapy. To this end, we engineered TNE@AHA_C implants consisting of a Mg–Zn alloy substrate functionalized with a multilayered coating: a corrosion-resistant MgF₂ underlayer, a polydopamine/polyethyleneimine adhesive interlayer, and an infection-responsive aldehyde-modified hyaluronic acid (AHA) hydrogel toplayer embedded with microbe-targeting Fe₃O₄ nanozymes (TNE). The implants demonstrated improved hydrophilicity and corrosion resistance and time-sequenced coating/substrate degradation. In infectious microenvironments, the TNE-embedded coating degraded preferentially, releasing nanozymes that catalytically generated bactericidal hydroxyl radicals to eradicate planktonic bacteria, intracellular pathogens, and biofilms, while stimulating M1 macrophage polarization for enhanced immunobactericidal activity. Subsequently, controlled substrate corrosion released bioactive ions (Mg²⁺, Zn²⁺) and H₂, which elicited M2 macrophage polarization and osteodifferentiation, while allowing favorable biocompatibility in vitro, in ovo, and in vivo. In a Staphylococcus aureus-infected rat femoral model, TNE@AHA_C effectively eliminated infection, mitigated inflammation and osteolysis, and enhanced osteoregeneration/osseointegration. This work establishes a sequential degradation-driven bioadaptive paradigm for implant-mediated microenvironment remodeling in infectious bone defects.