BACKGROUND: Individuals with diabetes mellitus (DM) are at an increased risk of vascular stiffness and atherosclerosis, which can predispose them to hypertension (HTN). Our study aims to analyze long-term mortality trends related to DM and HTN in the United States (US) and to identify vulnerable populations. METHODS: The CDC WONDER database was used to extract mortality data among adults (≥ 25 years of age) in the US who had concomitant DM and HTN. Age-adjusted mortality rates (AAMRs) were estimated and mortality trends were assessed using annual percentage change (APCs) with JoinPoint. RESULTS: A total of 2 769 118 deaths were attributed to DM and HTN in the US from 1999 to 2023. The AAMRs increased from 14.9 in 1999 to 66.8 in 2023 reflecting a 4.5-fold increase in mortality. A peak in mortality was observed during the COVID-19 pandemic with AAMR reaching 77.9 in with an APC of 15.7. Men had consistently higher AAMR compared to women (84.5 vs. 52.6 in 2023). Among racial/ethnic groups, non-Hispanic (NH) Black or African American individuals had the highest average AAMR, followed by Hispanic or Latino individuals, NH Other populations, and lastly the NH White individuals. The south had the highest AAMR among census regions and rural areas had higher mortality rates compared to urban areas (85.5 vs. 71.7). CONCLUSION: Our study shows a 4.5-fold increase in DM and HTN-related mortality in the United States from 1999 to 2023. Demographic and geographical disparities were evident with men, NH Blacks or African Americans, and rural areas at the highest risk reflecting the need for improved healthcare.