The study analyzed US death records from 1999–2023 from the CDC WONDER database, where diabetes mellitus (ICD-10 codes E10–E14) and depressive disorders (ICD-10 codes F32–F33, F41.2) were reported as underlying or contributing causes. National age-adjusted mortality rates (AAMRs) per 100,000 population were low and stable in the mid-to-late 2000s, but have increased since the late 2010s. Rates were higher in men than women and increased with age, peaking in those 85 and older. Non-Hispanic Americans/Alaska Natives had the highest AAMR, followed by non-Hispanic blacks and Hispanics; non-Hispanic whites and Asians had lower. Regionally, the West dominated with the highest rates, the Northeast with the lowest; nonmetropolitan counties outnumbered metropolitan ones, and states showed a three-fold difference between the top and bottom deciles. Findings show rising mortality and demographic-geographic disparities supporting targeted care strategies.