The use of sulfonamides (SAs) leads to residual environmental pollution. Bacteria play a crucial role in the degradation of SAs, and microbial consortium offers advantages over single bacterium. However, the complexity of the degradation processes and interaction mechanisms within such consortia remains a mystery. Here, a consortium named ACJ, comprising sp. HA-1, sp. HC-1, and sp. HAEJ-1, isolated from activated sludge in the wastewater treatment facilities of pharmaceutical plants, was identified as capable of degrading various SAs. Here, a pure culture of sp. HA-1, which plays a key role in SAs degradation, was obtained with the auxotrophic requirements (ARs) provided by strains HC-1 and HAEJ-1. Strain HA-1 initiated the breakdown of SAs molecules, releasing heterocyclic structure products and trihydroxybenzene (HHQ), which were further degraded and used for growth by strain HAEJ-1. Genomic, transcriptomic, and metabolomic analyses indicated that genes related to nucleotide repair, ABC transporters, quorum sensing, the TCA cycle, and the cell cycle in strain HA-1 were upregulated during co-culture compared to cultures without the other two strains, which indicated that certain factors of strains HC-1 and HAEJ-1 activated the growth of strain HA-1. These results demonstrate a bidirectional ecological relationship of cross-feeding and co-degradation among the consortium members. Overall, this study provides new insights into the mechanisms of microbial interaction and co-degradation in sulfonamides-contaminated environments.IMPORTANCESulfonamides (SAs) are widely used antibiotics that have significantly harmed the ecological environment, emerging as a new environmental pollutant. Currently, limited research exists on the mechanisms of microbial consortium interaction and co-degradation of environmental pollutants. Addressing challenges in environmental pollutant degradation, this study isolated a bacterial consortium, ACJ, dominated by the challenging-to-culture sp. HA-1 from a sewage treatment plant and unveiled their interaction and co-degradation mechanisms during SAs degradation. Toxicological experiments demonstrated that the degradation of SAs by consortium ACJ substantially reduced environmental damage. These findings offer new insights into the collaborative mechanisms of the consortium of environmental pollutant-degrading microbial consortia and provide valuable microbial resources for the remediation of antibiotic-contaminated environments.