A novel laboratory-scale aerobic submerged membrane bioreactor integrating sponge-plastic biocarriers (SPSMBR) was conducted to study the removal and degradation mechanisms of sulfonamide antibiotics (SAs). Experimental results indicated that SPSMBR had a better removal of sulfadiazine (91% SDZ) and sulfamethoxazole (88% SMZ) than that of a conventional aerobic submerged membrane bioreactor (CSMBR) (76% SDZ and 71% SMZ, respectively). Material balance calculations suggested that biodegradation is the primary removal mechanism of SDZ and SMZ. Protein (tyrosine-like materials) significantly affected the removal of SAs. Moreover, the SPSMBR exhibited its better performance in removing SAs due to more abundance of tyrosine-like materials. The 16S rRNA sequencing showed that biocarriers could promote the enrichment of slow growing bacteria, especially Thermomonas, associated with the removal of SAs. Valuable insights into the removal and degradation mechanisms of SAs in the SPSMBR systems are documented here.