Anaerobic sewage sludge capable of rapidly degrading tetrabromobisphenol A (TBBPA) was successfully acclimated in an anaerobic reactor over 280 days. During the period from 0 to 280 days, the TBBPA degradation rate (DR), utilization of glucose, and VSS were monitored continuously. After 280 days of acclimation, the TBBPA DR of active sludge reached 96.0% after 20 days of treatment in batch experiments. Based on scanning electron microscopy (SEM) observations and denaturing gradient gel electrophoresis (DGGE) determinations, the diversity of the microorganisms after 0 and 280 days in the acclimated anaerobic sewage sludge was compared. Furthermore, eleven metabolites, including 2-bromophenol, 3-bromophenol, 2,4-dibromophenol, 2,6-dibromophenol, tribromophenol and bisphenol A, were identified by gas chromatography–mass spectrometry (GC–MS). Moreover, the six primary intermediary metabolites were also well-degraded by the acclimated anaerobic sewage sludge to varying degrees. Among the six target metabolites, tribromophenol was the most preferred substrate for biodegradation via debromination. These metabolites degraded more rapidly than monobromide and bisphenol A. The biodegradation data of the intermediary metabolites exhibited a good fit to a pseudo-first-order model. Finally, based on the metabolites, metabolic pathways were proposed. In conclusion, the acclimated microbial consortia degraded TBBPA and its metabolites well under anaerobic conditions.