Both the academic and the policy community are calling for wider application of mixed methods research, suggesting that combined use of quantitative and qualitative methods is most suitable to assess and understand the complexities of health interventions. In spite of recent growth in mixed methods studies, limited efforts have been directed towards appraising and synthetizing to what extent and how mixed methods have been applied specifically to Health Policy and Systems Research (HPSR) in low- and middle-income countries (LMICs). We aimed at filling this gap in knowledge, by exploring the scope and quality of mixed methods research in the African context. We conducted a scoping review applying the framework developed by Arksey and O’Malley and modified by Levac et al. to identify and extract data from relevant studies published between 1950 and 2013. We limited our search to peer-reviewed HPSR publications in English, which combined at least one qualitative and one quantitative method and focused on Africa. Among the 105 studies that were retained for data extraction, over 60% were published after 2010. Nearly 50% of all studies addressed topics relevant to Health Systems, while Health Policy and Health Outcomes studies accounted respectively for 40% and 10% of all publications. The quality of the application of mixed methods varied greatly across studies, with a relatively small proportion of studies stating clearly defined research questions and differentiating quantitative and qualitative elements, including sample sizes and analytical approaches. The methodological weaknesses observed could be linked to the paucity of specific training opportunities available to people interested in applying mixed methods to HPSR in LMICs as well as to the limitations on word limit, scope and peer-review processes at the journals levels. Increasing training opportunities and enhancing journal flexibility may result in more and better quality mixed methods publications.