IMPORTANCE: It is critical to evaluate the risk of comorbid psychiatric diagnoses to meet the needs of individuals with autism spectrum disorder (ASD). OBJECTIVE: To examine whether individuals with ASD are at greater risk for comorbid diagnoses of depression, anxiety, or bipolar disorder. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from a population-based birth cohort of 31 220 individuals born in Olmsted County, Minnesota, from January 1, 1976, to December 31, 2000. Patients with research-identified ASD were previously identified using a multistep process that evaluated signs and symptoms abstracted from medical and educational records. For each of the 1014 patients with ASD, 2 age- and sex-matched referents who did not meet criteria for ASD were randomly selected from the birth cohort (n = 2028). Diagnosis codes for anxiety, depression, and bipolar disorders were electronically obtained using the Rochester Epidemiological Project records-linkage system. Data analysis was performed from July 1, 2018, to April 1, 2019. MAIN OUTCOMES AND MEASURES: Cumulative incidence of clinically diagnosed depression, anxiety, and bipolar disorder through early adulthood in individuals with ASD compared with referents. RESULTS: A total of 1014 patients with ASD (median age at last follow-up, 22.8 years interquartile range, 18.4-28.0 years; 747 73.7% male; 902 89.0% white) and 2028 referents (median age at last follow-up, 22.4 years interquartile range, 18.8-26.2 years; 1494 73.7% male; 1780 87.8% white) participated in the study. Patients with ASD were significantly more likely to have clinically diagnosed bipolar disorder (hazard ratio HR, 9.34; 95% CI, 4.57-19.06), depression (HR, 2.81; 95% CI, 2.45-3.22), and anxiety (HR, 3.45; 95% CI, 2.96-4.01) compared with referents. Among individuals with ASD, the estimates of cumulative incidence by 30 years of age were 7.3% (95% CI, 4.8%-9.7%) for bipolar disorder, 54.1% (95% CI, 49.8%-58.0%) for depression, and 50.0% (95% CI, 46.0%-53.7%) for anxiety. Among referents, cumulative incidence estimates by 30 years of age were 0.9% (95% CI, 0.1%-1.7%) for bipolar disorder, 28.9% (95% CI, 25.7%-32.0%) for depression, and 22.2% (95% CI, 19.3%-25.0%) for anxiety. CONCLUSIONS AND RELEVANCE: The findings suggest that individuals with ASD may be at increased risk for clinically diagnosed depression, anxiety, and bipolar disorder compared with age- and sex-matched referents. This study supports the importance of early, ongoing surveillance and targeted treatments to address the psychiatric needs of individuals with ASD.