Solid-phase denitrification (SPD) has been used in wastewater treatment plant effluent to enhance nitrate removal, and antibiotics co-existing in the effluent is a common environmental problem. In this study, it was systematically investigated the effect of single trace sulfamethoxazole (SMX)/trimethoprim (TMP) and their mixture on microbial denitrification performance, the antibiotics removal, and antibiotics resistance genes (ARGs) in corncob supported SPD system. The average denitrification rate was improved by 46.90% or 61.09% with single 50 µg/L SMX or TMP, while there was no significant inhibition with mixed SMX and TMP. The abundance of dominant denitrifiers (Comamonadaceae family and Azospia) and fermentation bacteria (Ancalomicrobium) were consistent with the denitrification performance of different antibiotics groups. Single SMX and TMP achieved relatively higher denitrification gene and enzyme abundance. Mixed SMX and TMP improved the denitrification gene copies, but they reduced the key denitrification enzymes except for EC 1.7.7.2. Additionally, the removal efficiency of TMP (56.70% ± 3.18%) was higher than that of SMX (25.44% ± 2.62%) in single antibiotic group, and the existence of other antibiotics (i.e. SMX or TMP) had no significant impact on the TMP or SMX removal performance. Biodegradation was the main removal mechanism of SMX and TMP, while sludge and corncob adsorption contributed a little to their removal. SMX had the risk of sulfanilamide resistance genes (SRGs) dissemination. Furthermore, network analysis indicated that Niveibacterium and Bradyrhizobium were the potential hosts of SRGs, which promoted the horizontal transmission of ARGs.