Background: The population of French Guiana is young, poor, and multicultural. We thus hypothesized that the epidemiology of depression and its care may differ from that in mainland France. We took the opportunity of the Mental Health in the General Population survey to estimate the overall prevalence of depression in the general population and its prevalence in different sociodemographic subgroups using the MINI interview. Methods: The cross-sectional survey was conducted 881 persons aged > 17 years were interviewed and analyzed. Results: There were 151 current depressive episodes setting the prevalence at 17.1% (95% confidence interval = 14.8–19.8%). For recurrent depression, the prevalence was 7.9% (95% confidence interval = 6.3–9.9%). The prevalence of current depression was independently greater among younger age groups than those aged 65 or more (age ≤ 25 years (aPR = 4.4 (95% CI = 1.5–12.3), p = 0.004); age 26–35 years (aPR = 3.3 (95% CI = 1.2–9), p = 0.01) persons who did not complete primary education (aPR = 1.9 (95% CI = 1–3.5), p = 0.04), those who earned less than EUR 840 (aPR = 2 (95% CI = 1.1–3.8), p = 0.04), and those who were separated or divorced relative to those married or in a couple (aPR = 2.2 (95% CI = 1.1–4.5), p = 0.02). For recurrent depressive episodes, multiple Poisson regression found that younger age categories relative to those aged > 65 years ≤ 25 years (aPR = 9.9 (95% CI = 1.1–85.9), p = 0.04), those aged 26–35 years (aPR = 9.3 (95% CI = 1.1–78.9), p = 0.04), and female sex (aPR = 2.04 (95% CI = 1.2–3.4), p = 0.007) were independently associated with the outcome. Conclusions: Depression is more frequent in French Guiana than in mainland France and is strongly associated with youth and poverty.