The objective of this study was to compare the current prevalence and co-occurrence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, alcohol and drug use disorders and mood, anxiety, and personality disorders among whites, blacks, Native Americans, Asians, and Hispanics in a large representative sample of the US population. Striking mental health disparities were observed in the prevalences of psychiatric disorders, especially among Native Americans. Disparities in psychiatric comorbidity differed from those associated with prevalence. Most significantly, the association between alcohol disorders and personality disorders was significantly greater among Asians relative to whites, blacks, and Native Americans, despite lower prevalences of these disorders among Asians. Taken together, the results of this study highlight the need of future studies that help unravel the risk factors underlying the disparities in both prevalence and comorbidity of psychiatric disorders observed among race-ethnic groups in the United States.