The purpose of this article was to describe patterns of poor mental health/depression (PMHD) in a national sample of college students and the relationships among PMHD, alcohol consumption, harm, and abuse. Responses to mailed questionnaires completed by a random sample of 27,409 students at 119 colleges were analyzed using logistic regression. Nationally, 4.8% of students reported PMHD. The average college prevalence was 5.01% (range, 0.68% to 13.23%). Students with PMHD were more likely than their peers to be female, nonwhite, and from low socioeconomic status families; less likely to report never drinking; as likely to report frequent, heavy, and heavy episodic drinking; and more likely to report drinking to get drunk. Students with PMHD—especially females—were more likely to report drinking-related harms and alcohol abuse. College is a critical context for studying youth mental health. The interrelationship of mental health problems and their clustering by group and college are important considerations for prevention and treatment.