Background <p>Type 2 diabetes mellitus (T2DM) related mortality trends remain understudied among younger adults in the United States (US). This study aims to bridge this gap by using data from a large national database of mortality statistics.</p> Methods <p>Death certificate data from 1999 to 2020 were extracted from the CDC WONDER database for all the fatalities among US adults aged 25 to 64 years, where T2DM was listed as the underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) per 1&#xa0;million persons were calculated, and temporal mortality trends were evaluated by computing annual percent change (APC) in AAMRs using the Joinpoint log-linear regression model.</p> Results <p>A total of 272,155 T2DM-related deaths occurred among US adults aged 25–64 years from 1999 to 2020. The overall AAMR significantly increased from 37.6 in 1999 to 138.36 by 2020 with an APC of 4.8 (<i>p</i> &lt; 0.01). Males had higher AAMR than females (80.13 vs. 51.20), and adults aged 55–64 years had a higher mortality rate than younger age groups. Among races, non-Hispanic American Indians/Alaska Natives had the highest AAMR (177.09). Mortality rates showed a significant upward trend across all genders, age groups, and racial subgroups. Nonmetropolitan areas had higher AAMR than metropolitan areas (83.08 vs. 61.97). AAMR varied substantially by state, with the highest AAMR in West Virginia (140.39) and the lowest in Massachusetts (23.06).</p> Conclusion <p>T2DM-related mortality has significantly increased among younger US adults over the last two decades. Higher mortality rates were observed among males, NH American Indians, and residents of rural areas and the Western regions.</p> Graphical Abstract <p></p>