In this study, the effect of arsenic on the sulfamethoxazole (SMX) removal efficiency and microbial community structure was investigated over 60 days using the SBR process. The results showed that the presence of arsenic had no significant impact on the system performance, the removal efficiencies of two reactors, R1 (the control test) and R2 (with the addition of arsenic), were 13.36 ± 5.71 and 14.20 ± 5.27%, which were attributed to the adsorption of SMX by fulvic acid-like substances and tryptophan-like proteins of extracellular polymeric substances. Compared to the seed sludge, the species number indicated that R2 possessed the richer diversity, while R1 possessed the lower diversity on day 60, which might be relative to the transferring of antibiotic resistance genes (ARGs) in sludge bacterial communities; the minute amounts of arsenic could make the relative levels of Sul1 and Sul2 genes which encode ARGs of sulfonamides in R2 (2.07 and 2.47%) be higher than that in R1 (1.65 and 1.27%), which made the bacterial community of the R2 system more adaptable to SMX stress. Therefore, the minute amounts of arsenic weakened the effect of SMX on the system and enhanced the stability of the microbial community structure.