Purpose Studies show health professional students have a high prevalence of depression. Dental students are especially susceptible due to the burden of the highest debt, exposure to bloodborne pathogens and chronic pain frequency. However, few studies on depression among U.S. dental students exist. This study aims to determine: (1) the difference in depression prevalence between U.S. dental students, the general population, and medical students; and (2) demographic and lifestyle characteristics associated with depressive symptoms in dental students. Methods Researchers surveyed dental students in California in 2018 using a 36‐ item questionnaire. The Patient Health Questionnaire (PHQ‐9), a validated diagnostic screening tool, measured depressive symptoms suggesting clinically significant moderate to severe depression. Additionally, participants answered demographic and lifestyle characteristics questions. Data analysis included bivariable chi‐square tests and multivariable logistic regression. Results The response rate was 19.1%. The crude depressive symptom prevalence (27.7%) was similar to that of depression in medical students (27.2%) and higher than the U.S. population (7.7%). Bivariable analysis indicated several characteristics significantly associated (P ≤ 0.05) with moderate to severe depressive symptoms in dental students, including experience of injury/pain, financial insecurity, self‐reported minority status, perception of meaningful work, and year in school. Multivariable logistic regression modeling estimated 5 well‐being categories as significantly associated with higher odds of not having major depressive symptoms. Conclusions Prevalence of depressive symptoms among California dental students is similar to depression in medical students and higher than the general population. Results suggest a significant proportion of dental students experience moderate to severe depression and require accessible resources.