Antibiotics often are input to biological-treatment systems for domestic sewage, and they can inhibit nitrifying bacteria and impair nitrification performance. In this work, activated sludge was acclimated to either a high or a low ammonium concentration in the continuous presence of 10 mg/L the antibiotic sulfamethoxazole (SMX). The high ammonium concentration led to nitrifying activated sludge (NAS), while the low ammonium concentration led to conventional activated sludge (CAS). After acclimation, the NH4+-removal rate for NAS was 8-fold greater than the rate for CAS when 10 mg/L SMX also was present in the medium. NAS also biotransformed SMX faster than did CAS. The removal kinetics for NH4+ and SMX were well represented by the Aiba self-inhibition model: The NAS biomass had a much faster maximum removal rate for NH4+, and it had better affinity for NH4+ and less inhibition from SMX. The NAS biomass also had faster biotransformation kinetics for SMX, with the main impact being a much faster maximum specific biotransformation rate (rmax). Analysis of microbiological community documented that the NAS biomass was enriched in nitrifying bacteria and also had more heterotrophic bacteria likely to be able to biotransform SMX.