INTRODUCTION: Depression is the leading cause of disability around the world, and it has been increasingly affecting young people. This study evaluates the prevalence and factors associated with major depression in university students, with emphasis on the influence of the academic field, chosen study area and the environment they are inserted. METHODS: A census of students who entered the university in the first semester of 2017 was held at a university in Southern Brazil. The outcome of major depressive episode was evaluated using the Patient Health Questionnaire-9, considered when the individual had five or more depressive symptoms for at least one week. Its prevalence was estimated, and the associated factors were examined by the hierarchical multivariable analysis using the Poisson regression model. RESULTS: A total of 32% (95% confidence interval 29.9–34.2) of university students presented a major depressive episode, and the problem was more frequent among women (prevalence ratio [PR] = 1.59); people aged 21 to 23 years (PR = 1.24); those with a family history of depression (PR = 1.27); minorities’ sexual orientation (homosexuals, PR = 1.64, and bisexuals, PR = 1.69); who lived with friends or colleagues (PR = 1.36); students in the area of applied social and human sciences (PR = 1.28), and linguistics, language and literature, and art (PR = 1.25). The worst academic performance (PR = 2.61), alcohol abuse (PR = 1.25), and illicit drug use (PR = 1.30) were also positively associated with major depressive episode. CONCLUSION: In addition to individual, family, and behavioral aspects, already described as risk factors for major depressive episodes in the general population, academic aspects also influence the occurrence of depression among university students. Considering the high prevalence of major depressive episode and its negative impact on health, public and institutional policies are necessary to focus on students’ mental health promotion and care.