Objectives There is a growing interest in health technology assessment and economic evaluations in developing countries such as Ethiopia. The objective of this study was to derive an EQ-5D-5L value set from the Ethiopian general population to facilitate cost utility analysis. Methods A nationally representative sample (N = 1050) was recruited using a stratified multistage quota sampling technique. Face-to-face, computer-assisted interviews using the EuroQol Portable Valuation Technology (EQ-PVT) protocol of composite time trade-off (c-TTO) and discrete choice experiments (DCEs) were undertaken to elicit preference scores. The feasibility of the EQ-PVT protocol was pilot tested in a sample of the population (n = 110). A hybrid regression model combining c-TTO and DCE data was used to estimate the final value set. Results In the pilot study, the acceptability of the tasks was good, and there were no special concerns with undertaking the c-TTO and DCE tasks. The coefficients generated from a hybrid model were logically consistent. The predicted values for the EQ-5D-5L ranged from −0.718 to 1. Level 5 anxiety/depression had the largest impact on utility decrement (−0.458), whereas level 5 self-care had the least impact (−0.222). The maximum predicted value beyond full health was 0.974 for the 11112 health state. Conclusions This is the first EQ-5D-5L valuation study in Africa using international valuation methods (c-TTO and DCE) and also the first using the EQ-PVT protocol to derive a value set. We expect that the availability of this value set will facilitate health technology assessment and health-related quality-of-life research and inform policy decision making in Ethiopia.