The growing occurrence of antibiotics in water environment is causing increasing concern. To investigate the impact of frequently detected sulfadiazine on the formation of aerobic granular sludge, four sequencing batch reactors (SBRs) were set up with different environmentally relevant concentrations of sulfadiazine. Results showed that sulfadiazine pressure could lead to larger and more compact sludge particles and cause slight effect on reactor performance. Presence of sulfadiazine apparently increased the extracellular polymeric substances (EPS) secretion of microorganisms. Quantitative polymerase chain reaction (qPCR) showed that the abundances of sulfanilamide resistance genes in sludge increased with addition of sulfadiazine significantly. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional genes, results showed that sulfadiazine led to an increase of specific functional genes. Thereby, it concluded that microorganisms could change the community structure by acclimating of functional bacteria and antibiotic resistance species to adapt to the antibiotic stress.