Minimizing antimicrobial use is a recommended strategy to reduce the evolution and spread of antibiotic resistance; however, efficacy is elusive to measure. Wastewater-based surveillance provides a promising means to relate trends in microbial community antibiotic resistance profiles as a function of interventions and other factors. We examined influent sewage metagenomes for two neighboring wastewater treatment plants (WWTPs) serving a university and a nearby community. We compared antibiotic resistance gene (ARG) profiles as a function of diagnoses of COVID-19 and other illnesses, antibiotic use, antibiotic/antimicrobial and disinfectant/quaternary ammonium compound concentrations, and COVID-19-related behavioral shifts. Diversity and abundances of ARGs unique to the corresponding sewage were consistently higher for the community WWTP, but converged in 2022 when antibiotic prescriptions surged in the university zip code. Decreases in ARG diversity/abundance were not apparent during periods of decreased antibiotic usage, indicating that extended times may be required for wastewater ARG signals to attenuate following interventions.