INTRODUCTION: Ensuring universal availability and accessibility of medicines and supplies is critical for national health systems to equitably address population health needs. In sub-Saharan Africa (SSA), this is a recognised priority with multiple medicines pricing policies enacted. However, medicine prices have remained high, continue to rise and constrain their accessibility. In this systematic review, we aim to identify and analyse experiences of implementation of medicines pricing policies in SSA. Our ambition is for this evidence to contribute to improved implementation of medicines pricing policies in SSA. METHODS AND ANALYSIS: We will search: Medline, Web of Science, Scopus, Global Health, Embase, Cairn.Info International Edition, Erudit and African Index Medicus, the grey literature and reference from related publications. The searches will be limited to literature published from the year 2000 onwards that is, since the start of the Millennium Development Goals.Published peer-reviewed studies of implementation of medicines pricing policies in SSA will be eligible for inclusion. Broader policy analyses and documented experiences of implementation of other health policies will be excluded. The team will collaboratively screen titles and abstracts, then two reviewers will independently screen full texts, extract data and assess quality of the included studies. Disagreements will be resolved by discussion or a third reviewer. Data will be extracted on approaches used for policy implementation, actors involved, evidence used in decision making and key contextual influences on policy implementation. A narrative approach will be used to synthesise the data. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guideline. ETHICS AND DISSEMINATION: No ethics approvals are required for systematic reviews.Results will be disseminated through academic publications, policy briefs and presentations to national policymakers in Ghana and mode widely across countries in SSA. PROSPERO REGISTRATION NUMBER: CRD42020178166.