There is a growing need to mitigate the discharge of extracellular antibiotic resistance genes (ARGs) from municipal wastewater treatment systems. Here, molecularly-imprinted graphitic carbon nitride (MIP-C 3 N 4 ) nanosheets were synthesized for selective photocatalytic degradation of a plasmid-encoded ARG (bla NDM-1 , coding for multidrug resistance New Delhi metallo-β-lactamase-1) in secondary effluent. Molecular imprinting with guanine enhanced ARG adsorption, which improved the utilization of photogenerated oxidizing species to degrade bla NDM-1 rather than being scavenged by background nontarget constituents. Consequently, photocatalytic removal of bla NDM-1 in secondary effluent with MIP-C 3 N 4 (k = 0.111 ± 0.028 min −1 ) was 37 times faster than with bare graphitic carbon nitride (k = 0.003 ± 0.001 min −1 ) under UVA irradiation (365 nm, 3.64 × 10 −6 Einstein/L•s). MIP-C 3 N 4 can efficiently catalyze the fragmentation of bla NDM-1 , which decreased the potential for ARG repair by transformed bacteria. Molecular imprinting also changed the primary degradation pathway; electron holes (h + ) were the predominant oxidizing species responsible for bla NDM-1 removal with MIP-C 3 N 4 versus free radicals (i.e., •OH and O 2 − ) for coated but nonimprinted C 3 N 4 . Overall, MIP-C 3 N 4 efficiently removed bla NDM-1 from secondary effluent, demonstrating the potential for molecular imprinting to enhance the selectivity and efficacy of photocatalytic processes to mitigate dissemination of antibiotic resistance from sewage treatment systems.