OBJECTIVES: To estimate the proportion of adult primary care outpatients who are clinically detected and initiate treatment for depression and alcohol use disorder (AUD) in low-income and middle-income country (LMIC) settings. DESIGN: Five cross-sectional studies. SETTING: Adult outpatient services in 36 primary healthcare facilities in Sodo District, Ethiopia (9 facilities); Sehore District, India (3); Chitwan District, Nepal (8); Dr Kenneth Kaunda District, South Africa (3); and Kamuli District, Uganda (13). PARTICIPANTS: Between 760 and 1893 adults were screened in each district. Across five districts, between 4.2% and 20.1% screened positive for depression and between 1.2% and 16.4% screened positive for AUD. 96% of screen-positive participants provided details about their clinical consultations that day. PRIMARY OUTCOMES: Detection of depression, treatment initiation for depression, detection of AUD and treatment initiation for AUD. RESULTS: Among depression screen-positive participants, clinical detection of depression ranged from 0% in India to 11.7% in Nepal. Small proportions of screen-positive participants received treatment (0% in Ethiopia, India and South Africa to 4.2% in Uganda). Among AUD screen-positive participants, clinical detection of AUD ranged from 0% in Ethiopia and India to 7.8% in Nepal. Treatment was 0% in all countries aside Nepal, where it was 2.2%. CONCLUSIONS: The findings of this study suggest large detection and treatment gaps for adult primary care patients, which are likely contributors to the population-level mental health treatment gap in LMIC. Primary care facilities remain unfulfilled intervention points for reducing the population-level burden of disease in LMIC.