Objective: Poverty is linked to poor mental health, and stress is a key pathway. Most existing stress scales were developed in high-income settings. We use primary data collected from three large population-based studies in Ghana and Tanzania to examine the performance and psychometric properties of a new measure of self-perceived stress, the Enhanced Life Distress Inventory (ELDI). Methods: Development of the ELDI was informed by an exploratory qualitative study implemented among youth and adolescents in Ghana, Malawi, and Tanzania and structured following the Life Distress Inventory (LDI). We implemented the ELDI in three ongoing longitudinal impact evaluations involving quantitative household surveys in two studies in Tanzania and in one in Ghana to evaluate its performance and psychometric properties. Findings: Sample sizes ranged from N = 608 to N = 2,458, with variation in gender, age, and geographic location. Exploratory factor analysis uncovered three underlying factors of the ELDI, which justified the use of three sub-scales: economic and health-related well-being, risk/security, and social relations. Further analysis demonstrated that the ELDI has adequate psychometric properties, including internal consistency, and construct validity. Conclusion: A major contribution of the ELDI is its development in and for LMIC settings and its ability to assess different areas (life domains) of distress. This multi-sectoral lens gives the scale the potential to examine not only programmes targeting stress, but also those targeting sources of stress, and to examine whether they improve stress and mental health via those pathways. More testing of the ELDI’s performance and psychometric properties is needed in additional settings.