Although Australia maintains relatively low national rates of antimicrobial resistance (AMR), considerable geographic disparities exist. Particularly, the Northern Territory suffers disproportionately high AMR burdens despite low reported antimicrobial prescribing through the PBS/RPBS national reporting system. This mismatch highlights systematic under-reporting of national prescription monitoring, which often overlooks alternative sources of antimicrobial access and use in remote communities, leaving critical gaps in tracking antimicrobial use alongside AMR evolution and spread. In this study, wastewater-based epidemiology (WBE) combined with clinical antibiotic susceptibility data from a phenotypic AMR surveillance program was used to estimate antimicrobial use and AMR prevalence in Australia and to assess temporal trends in the Northern Territory (2012–2023). Over 12 years, AMR to six common antibiotics has progressively increased among three priority pathogens in the Northern Territory. WBE-estimates of antimicrobial use were generally consistent with prescriptions across all Australian States/Territories, except in the Northern Territory. The Northern Territory had the second-highest rate of antimicrobial use identified in WBE, but the lowest prescriptions reported to the PBS/RPBS. Additionally, prescriptions suggest a steady decline in antimicrobial use over time, while WBE revealed a marked increase in 2020, with usage peaking in 2021 during the COVID-19 pandemic. The divergence between declining prescriptions and increasing WBE-estimated antimicrobial use in the Northern Territory highlights systematic under-representation and critical surveillance blind spots. WBE offers an invaluable complement to traditional prescription data sources, particularly in remote settings that are systematically underrepresented in prescription datasets. Integrating WBE with clinical AMR surveillance could provide a more comprehensive understanding of antimicrobial use and its impact on AMR across Australia’s Northern Territory, supporting more equitable medication policy for remote and First Nations populations.