The　microbial　communities　of　activated　sludge　could　be　affected　by　antibiotics　pollution.　However,　it　is　unclear　that　how　the　historical　antibiotic　stress　feedback　to　the　later　responses　of　microbes　and　antibiotic　resistance　genes　(ARGs)　to　combined　antibiotics　stress　by　leaving　their　imprint　on　activated　sludge　(“legacy　effect”).　In　order　to　conceptualize　the　role　of　antibiotic　legacy　effects,　sulfamethoxazole　(SMX)　or　trimethoprim　(TMP)　was　selected　as　historical　stress　to　investigate　responses　of　activated　sludge　to　combined　SMX　and　TMP　stress　(0.005–30　mg/L).　Ammonia　removal　was　affected　by　legacy　of　activated　sludge　delivered,　which　increased　with　the　increase　of　historical　antibiotic　concentrations,　but　it　was　less　affected　by　the　legacy　of　antibiotic　type　stress.　Changes　of　aromatic　protein-like　substances　and　soluble　microbial　by-products　in　soluble　microbial　product　(SMP)　and　tightly　bound　extracellular　polymeric　substances　(TB-EPS)　were　more　obvious　under　combined　SMX　and　TMP　stress,　which　could　reflect　the　dynamic　response　of　microorganisms　to　antibiotics　stress.　Legacy　effects　affected　response　of　structure　and　composition　of　microbial　community　to　later　antibiotic　stress.　ARGs　could　produce　positive　feedback　on　the　increase　of　relative　abundance　of　hosts　under　antibiotics　stress　to　occupy　the　niche　of　bacteria　with　high　relative　abundance,　especially　genera　(Taibaiella,　Hydrogenophaga,　et　al.)　with　low　proportion　but　carrying　multiple　ARGs　(mdtD,　mdtG,　acrD).　Overall,　legacy　of　activated　sludge　delivered　is　able　to　change　its　responses　to　antibiotics　stress,　and　the　occurrence　of　ARGs　can　drive　enrichment　of　their　potential　hosts.　©　2022　Elsevier　Ltd