BACKGROUND: Acute myocardial infarction (AMI) with essential hypertension (EH) and secondary hypertension (SH) remains a leading cause of mortality. Despite the overall decline, disparities in mortality trends across age group, gender, urbanization, racial, and regional subgroups remain underexplored. METHODS: Mortality data from the CDC WONDER (2000-2024) were analyzed for AMI (ICD-10 I21) as the primary cause of death and EH (ICD-10 I10) and SH (ICD-10 I15.0, I15.9) as a contributing factor in individuals aged ≥ 25 years. Age-adjusted mortality rates (AAMRs) were standardized to the US 2000 population. Joinpoint regression estimated annual percentage changes (APCs) with 95% confidence intervals (CIs). RESULTS: AMI with hypertension caused 842,646 deaths, with AAMR declining from 17.63 in 2000 to 12.26 in 2024. Overall, the AAMR showed a significant decline across the study period (AAPC: -1.71%). Males consistently had a higher mean AAMR (18.50) than females (11.82). Upward inflections were noted in the South region during 2018-2021 (APC: 11.17%; p = 0.004), Non-Hispanic Black individuals during 2018-2021 (APC: 9.45%; p = 0.053), metropolitan areas during 2018-2020 (APC: 7.71%; p = 0.038), and among adults aged 65-74 years during 2018-2021 (APC: 7.15%; p = 0.039). State-level variations were observed. CONCLUSION: Despite the overall decline, rising mortality trends were observed in the Southern region (2018-2021), metropolitan areas, and among individuals aged 65-74 years, highlighting emerging patterns and emphasizing the need for targeted interventions.