Purpose <p>We examined the associations between county-level endocrine-disrupting pesticide usage and breast cancer incidence, overall and by metropolitan status.</p> Methods <p>This ecological study used publicly available data from the United States Geological Survey on county-level agricultural pesticide usage (in kilograms). We focused on 38 pesticides with endocrine-disrupting properties relevant in breast cancer etiology, which were categorized by chemical class as follows: carbamates, neonicotinoids, organochlorines, organophosphates, phosphonates, pyrethroids, triazines, and other miscellaneous compounds. The analysis included 2,457 U.S. counties with data on pesticide usage (2001–2015) and age-adjusted breast cancer incidence rates (2016–2020), accounting for a latency period. Metropolitan status was assessed using the 2013 Rural–Urban Continuum Codes. Gamma regression models with a log-link function were used to estimate rate ratios (RR) and 95% confidence intervals (CI) between pesticides (per interquartile range increase) and age-adjusted breast cancer incidence rates, adjusting for county-level covariates including % smoking, % poverty, % unemployed, % no high school diploma, % uninsured, and residential mobility.</p> Results <p>Total median pesticide use was higher in rural vs. urban counties (17,523&#xa0;kg vs. 14,743&#xa0;kg; <i>p</i> &lt; 0.05), with some variation by pesticide class. Pesticide use was associated with slightly higher breast cancer incidence in rural counties (RR = 1.02 (95% CI 1.01, 1.03)), but not in urban counties (RR = 1.00 (95% CI 1.00, 1.00)) (<i>p</i>_int &lt; 0.001). Associations differed by pesticide type.</p> Conclusion <p>Results suggest modest positive associations between county-level endocrine-disrupting pesticide use and breast cancer incidence in rural U.S. counties, with variation by pesticide type. These findings highlight the need for further research to inform targeted prevention efforts.</p>