Background: Most research on the prevalence of mental disorders in primary care has been conducted in practices that serve middle- and upper-income patients. Objective: To determine the prevalence of major mental disorders in a primary care practice that serves a predominantly low-income immigrant patient population. Design: Cross-sectional survey; criterion standard. Setting: Urban general medicine practice. Participants: Systematic sample of consecutive adult patients with scheduled appointments. Of 1266 approached eligible patients, 1007 (80%) participated. Main Outcome Measures: PRIME-MD Patient Health Questionnaire major depression, generalized anxiety disorder, panic disorder, alcohol use disorder, and suicidal ideation; drug use disorder; functional status; work loss; family distress; and mental health treatment. Results: Major depression (18.9%), generalized anxiety (14.8%), panic (8.3%), and substance use (7.9%) disorders and suicidal ideation (7.1%) were highly prevalent. Many patients had more than 1 disorder (range, 36.3% [substance use disorder] to 76.9% [panic disorder]). In multivariate analyses, each disorder was significantly associated with an increase in impairment after controlling for demographic characteristics, perceived health, and the other disorders. A minority of patients with each disorder (range, 22.5% [substance use disorder] to 46.4% [panic disorder]) reported receiving mental health treatment in the last month. Conclusions: Clinically significant depression, anxiety, substance use, and suicidal ideation are quite common in this practice and associated with significant functional impairment. Primary care practices that serve poor urban immigrant populations have a critical need to provide access to mental health services.