Background: Breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer death among women in the United States (U.S.). While racial and ethnic disparities in outcomes are known, large population-based data on rural and urban disparities in breast cancer-related mortality are lacking. Methods: We retrieved de-identified data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) multiple causes of death database (years: 1999–2020) for females (aged 15 years and upwards) with “malignant neoplasm of breast” (ICD-10 C50) listed as “underlying cause of death”. We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population and assessed temporal trends in the average percent change (APC) of AAMRs applying the simplest model with a maximum of 3 joinpoints (using Joinpoint regression program 4.9.1.0). We conducted nonparallel pairwise comparisons to assess differences in trends between large metropolitan, medium to small metropolitan and rural areas (per National Center for Health Statistics Urban-Rural Classification Scheme, 2016) using average annual percentage change difference (AAPCD). Results: A total of 909,467 breast-cancer related deaths were analyzed between 1999-2020. We noted a decline in breast cancer related AAMR overall and across large metropolitan, small to medium metropolitan and rural areas (table). However, the decline in AAMR was significantly higher among large metropolitan areas as compared to small to medium metropolitan (AAPCD -0.3371, 95% CI -0.61, -2.4187, p=0.02) and rural areas (AAPCD: -0.48, 95% CI -0.79, -3.12, p=0.002). No significant difference in AAMR trend in small to medium metropolitan and rural areas was noted (AAPCD -0.15, 95% CI -0.37, 0.08, p=0.19). Conclusions: We demonstrate disparities in decline in breast cancer related AAMR between urban and rural areas. A significantly higher decline in AAMR among large metropolitan areas compared to medium to small metropolitan and rural areas suggests discrepancy in access to cancer care among populations. Further work is needed to develop strategies aimed at ensuring equitable cancer care access for all patients with breast cancer regardless of their geographical location.