Antimicrobial resistance (AMR) poses a global health threat, causing millions of deaths annually, with expectations of increased impact in the future. Wastewater surveillance offers a cost-effective, non-invasive tool to understand AMR carriage trends within a population. We monitored extended-spectrum β-lactamase producing Escherichia coli (ESBL-E. coli) weekly in influent wastewater from six wastewater treatment plants (WWTPs) in Switzerland (November 2021 to November 2022) to investigate spatio-temporal variations, explore correlations with environmental variables, develop a predictive model for ESBL-E. coli carriage in the community, and detect the most prevalent ESBL-genes. We cultured total and ESBL-E. coli in 300 wastewater samples to quantify daily loads and percentage of ESBL-E. coli. Additionally, we screened 234 ESBL-E. coli isolates using molecular methods for the presence of 18 ESBL-gene families. We found a population-weighted mean percentage of ESBL-E. coli of 1.9% (95% confidence interval: 1.8–2%) across all sites and weeks, which can inform ESBL-E. coli carriage. Concentrations of ESBL-E. coli varied across WWTPs and time, with higher values observed in WWTPs serving larger populations. Recent precipitations (previous 24/96 h) showed no significant association with ESBL-E. coli, while temperature occasionally had a moderate impact (P < 0.05, correlation coefficients approximately 0.40) in some locations. We identified blaCTX-M-1, blaCTX-M-9, and blaTEM as the predominant ESBL-gene families. Our study demonstrates that wastewater-based surveillance of culturable ESBL-E. coli provides insights into AMR trends in Switzerland and may also inform resistance. These findings establish a foundation for long term, nationally established monitoring protocols and provide information that may help inform targeted public health interventions.@en