BACKGROUND Prostate cancer is a leading cause of cancer-related mortality among men in the United States. Over the past two decades, the observed decline in prostate cancer mortality can be attributed to advancements in screening, early detection, and treatment. However, persistent disparities related to race, geography, and age highlight the need for targeted interventions to improve outcomes. METHODS This study evaluated trends in prostate cancer mortality among men aged 45 years and older in the United States, using data from CDC WONDER (1999-2020). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were analyzed using a log-linear regression model to calculate annual percentage changes (APCs) and 95 % confidence intervals. Crude rates were utilized to calculate APCs within specific age subgroups. RESULTS The AAMR related to prostate cancer significantly declined from 89.87 per 100,000 in 1999 to 52.92 in 2020. A steeper decline was noted from 1999 to 2013 (APC = -3.44), followed by a slower reduction thereafter (APC = -0.61), which coincided with changes in PSA screening guidelines introduced in 2012. African American men had the highest mortality rates but also experienced the most significant decline, decreasing from 199.91 per 100,000 in 1999 to 104.42 in 2020. Regional disparities evolved over time, with the West overtaking the South in mortality rates by 2020. Non-metropolitan areas consistently exhibited higher mortality rates compared to metropolitan regions. Age-stratified data indicated that AAMR increased with age, with the most notable declines seen in men aged 85 years and older. CONCLUSIONS Prostate cancer mortality in the United States has significantly decreased over the past 2 decades; however, the rate of progress has slowed in recent years. It is crucial to address racial, geographic, and age-related disparities to further reduce mortality and enhance equity in health outcomes.