Background: Work-related musculoskeletal disorders impose a significant and most often underappreciated burden to the individual, nation, healthcare system, and society as a whole. To the best of our knowledge, there is a lack of reliable estimates on the prevalence of work-related musculoskeletal disorders in Ethiopia. The objective of this study will be to assess the existing literature on the prevalence rates and determinant factors of work-related musculoskeletal disorders in Ethiopia.Method: We will search PubMed/MEDLINE, Embase, SCOPUS, PsycINFO, PEDro and Ebsco (from January 2000 onwards). Grey literature will be identified through searching Google Scholar and dissertation databases. Observational studies reporting on the prevalence of work-related musculoskeletal disorders among adult Ethiopians will be included. The primary outcome will be the prevalence of work-related musculoskeletal disorders. Secondary outcomes will be the prevalence of any risk factors in association with work-related musculoskeletal disorders. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Subgroup analyses will be conducted to explore the potential sources of heterogeneity (e.g. gender, sample size, type of occupation).Publication bias and heterogeneity between the included studies will also be assessed and reported.Discussion: This systematic review will provide a synthesis of the literature on the prevalence of work-related musculoskeletal disorders and their risk factors in Ethiopia. The results of this review could help the policymakers in occupational health and health care sectors in identifying priority areas for interventions in work-related musculoskeletal disorders and will also serve as a baseline for the decision-making processes of musculoskeletal health promotion, work exposure implementations, and prevention programs in workplaces. Systematic review registration: PROSPERO CRD42020164240