Objectives. Alcohol use disorder (AUD) and depression are the most commonly reported psychiatric comorbid conditions. We examined trends in the past-year prevalence of driving under the influence of alcohol (DUIA) among people with major depressive episodes (MDE), AUD, or both in the United States. Methods. We analyzed 543,573 individuals aged 18 years or older from the 2005-2019 National Surveys on Drug Use and Health (NSDUH). Multivariate logistic regression models were applied to examine the adjusted past-year prevalence of DUIA. To assess trends in DUIA over time, annual average percent change (AAPC) was calculated. Results. From 2005 to 2019, DUIA prevalence among US adults with MDE declined significantly from 18.1% to 9.4% (AAPC = -4.9). Decreasing trends in DUIA were also observed among those with AUD (from 55.4% to 37.8%, AAPC = -3.0) and among those with co-occurring MDE and AUD (from 58.3% to 38.8%, AAPC = -3.1). Compared to those with no AUD or MDE (from 8.42% to 3.99%, AAPC = -5.6), individuals with AUD and those with co-occurring MDE and AUD had significantly lower AAPCs. There was no significant AAPC difference between those with MDE and those with no AUD or MDE. Regarding sociodemographic characteristics, younger adults aged 18-34 exhibited the lowest AAPC among all diagnostic groups. Conclusions. From 2005 to 2019, DUIA prevalence declined significantly with varying rates of decrease across different diagnostic groups. Focused public health efforts are needed to engage high-risk groups that have shown a tendency toward less expedient reductions in DUIA.