Over one billion of the world’s population are smokers, with increasing tobacco use in low-and middle-income countries. However, information about the methodology of studies on tobacco control is limited. We conducted a literature search to examine and evaluate the methodological designs of published tobacco research in Sub-Saharan Africa (SSA) over the past 50 years. The first phase was completed in 2015 using PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials. An additional search was completed in February 2017 using PubMed. Only tobacco/smoking research in SSA countries with human subjects and published in English was selected. Out of 1796 articles, 447 met the inclusion criteria and were from 26 countries, 11 of which had one study each. Over half of the publications were from South Africa and Nigeria. The earliest publication was in 1968 and the highest number of publications was in 2014 (n = 46). The majority of publications used quantitative methods (91.28%) and were cross-sectional (80.98%). The commonest data collection methods were self-administered questionnaires (38.53%), interviews (32.57%), and observation (20.41%). Around half of the studies were among adults and in urban settings. We conclud that SSA remains a “research desert” and needs more investment in tobacco control research and training.