Abstract Purpose Indicators of prognosis should be considered to fully inform clinical decision making in the treatment of depression. This study examines whether self-rated health predicts long-term depression outcomes in primary care. Methods Our analysis was based on the first 5 years of a prospective 10-year cohort study underway since January 2005 conducted in 30 randomly selected Australian primary care practices. Participants were 789 adult patients with a history of depressive symptoms. Main outcome measures include risks, risk differences, and risk ratios of major depressive syndrome (MDS) on the Patient Health Questionnaire. Results Retention rates during the 5 years were 660 (84%), 586 (74%), 560 (71%), 533 (68%), and 517 (66%). At baseline, MDS was present in 27% (95% CI, 23%-30%). Cross-sectional analysis of baseline data showed participants reporting poor or fair self-rated health had greater odds of chronic illness, MDS, and lower socioeconomic status than those reporting good to excellent self-rated health. For participants rating their health as poor to fair compared with those rating it good to excellent, risk ratios of MDS were 2.10 (95% CI, 1.60–2.76), 2.38 (95% CI, 1.77–3.20), 2.22 (95% CI, 1.70–2.89), 1.73 (95% CI, 1.30–2.28), and 2.15 (95% CI, 1.59–2.90) at 1, 2, 3, 4, and 5 years, after accounting for missing data using multiple imputation. After adjusting for age, sex, multimorbidity, and depression status and severity, self-rated health remained a predictor of MDS up to 5 years. Conclusions Self-rated health offers family physicians an efficient and simple way to identify patients at risk of poor long-term depression outcomes and to inform therapeutic decision making.