The　co-exposure　of　antibiotics　has　important　effects　on　antibiotic　resistance　genes　(ARGs)　and　microbial　community　aggregation　in　wastewater　treatment　plants　(WWTPs).　However,　it　is　unclear　whether　differences　in　historical　antibiotic　exposure　stress　can　determine　responses　of　microbes　and　ARGs　to　combined　antibiotics.　By　selecting　a　high　concentration　(30　mg·L-1)　of　sulfamethoxazole　(SMX)　and　trimethoprim　(TMP)　as　historical　exposure　stress　conditions,　the　effects　of　SMX　and　TMP-combined　pollution　on　ARGs,　bacterial　communities,　and　their　interactions　were　explored　in　short-term　experiments.　Based　on　high-throughput　quantitative　PCR,　a　total　of　13　ARGs　were　detected,　and　the　absolute　abundance　was　2.21-5.42　copies·μL-1　(logarithm,　DNA,　the　same　below).　Among　them,　sul2,　ermB,　mefA,　and　tetM-01　were　the　main　subtypes　in　the　samples,　and　the　absolute　abundance　was　between　2.95　and　5.40　copies·μL-1.　The　combined　contamination　of　SMX　and　TMP　could　cause　the　enrichment　of　ARGs　and　mobile　genetic　elements　(MGEs);　however,　their　effects　on　each　subtype　were　different,　and　the　historical　legacy　effect　of　SMX　was　higher　than　that　of　TMP.　Under　the　different　exposure　histories,　the　co-occurrence　and　co-exclusion　patterns　existed　between　ARGs.　Moreover,　MGEs　(especially　intI-1)　were　significantly　correlated　with　sulfonamides　(sul1　and　sul2),　tetracyclines[tet(32)],　and　macrolide-lincosamide-streptogramin　(MLSB)　resistance　genes　(ermB).　Based　on　the　full-scale　classification　of　microorganisms,　it　was　found　that　the　microbial　community　structure　of　various　groups　responded　differently　to　combined　pollution,　and　the　conditionally　abundant　taxa　(CAT)　were　obviously　enriched.　Thauera,　Pseudoxanthomonas,　and　Paracoccus　were　the　dominant　resistant　bacterial　genera.　Furthermore,　a　total　of　31　potential　hosts　of　ARGs　were　identified　with　network　analysis,　which　were　dominated　with　conditionally　rare　taxa　(CRT).　Particularly,　Candidatus_Alysiosphaera　and　Fusibacter　were　positively　correlated　with　most　of　the　ARGs,　being　the　common　protentional　hosts.　Importantly,　some　rare　genera　(RT,　Variibacter,　Aeromonas,　Cloacibacterium,　etc.)　were　potential　hosts　of　transposon　IS613,　which　played　an　important　role　in　the　proliferation　and　spread　of　ARGs.　In　conclusion,　this　study　revealed　the　legacy　effects　of　historical　antibiotic　stress　on　ARGs　and　their　hosts,　which　could　provide　new　ideas　and　theoretical　basis　for　reducing　ARGs　pollution　in　WWTPs.