The ecological risks brought by sulfadiazine (SDZ) residues in the environment have put forward requirements for efficient antibiotic treatment technologies. In this study, biogenic manganese oxides (BMOs) were synthesized using the bacterium Stenotrophomonas maltophilia DT1, and a BMO/syringaldehyde (SYR) system was constructed for SDZ degradation to investigate its performance, mechanism, and potential application. Results showed that the DT1-synthesized BMO contained Mn (II/III/IV) and defect-related oxygen species, which enabled the BMO to participate in SYR activation and SDZ transformation. A total of 99.67% of 10 mg/L SDZ was removed within 3 h under optimized conditions. Humic acid and most environmental ions had no significant interference with the system, except for slight inhibition by Fe³⁺ and Mn²⁺. Three degradation pathways of SDZ were elucidated through the identification of five transformation products and density functional theory calculations. ECOSAR toxicity prediction and growth inhibition of Escherichia coli revealed that the degradation products exhibited significantly reduced toxicity. Furthermore, the BMO exhibited 4.41–17.47 times higher SYR-mediated SDZ transformation efficiency than chemically synthesized manganese oxide (CMO) and showed good performance in reuse tests and real water matrices. This study provides an efficient and eco-friendly green technology for the remediation of SDZ pollution in aquatic environments and provides potential support for the removal of refractory pollutants mediated by BMO.