BACKGROUND: Mycobacterium tuberculosis complex (MTBC) and its human host are the most competent organisms with co-evolutionary trajectory. This review determined the phylogeography, clinical phenotype-related genotype and transmission dynamics of MTBC in Africa.METHODS: Spoligotyping and mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) based articles from Africa published in the English language were included. Articles were retrieved from PubMed and Scopus on 12 May 2018.RESULTS: In Africa, respectively 92% and 7% of tuberculosis (TB) cases were caused by M. tuberculosis and M. africanum. Among M. tuberculosis lineages (L), L4 was the predominant, at 67%, followed by L3/Central Asian (CAS; 10%). L7/ETH1 and L5/6/Maf were restricted to the Horn and Western Africa, respectively. L4.6/SIT37, H37Rv like, L4.1.2/Haarlem and H3-Ural were proportionally more frequent among tuberculous lymphadenitis (TBLN) than among pulmonary tuberculosis (PTB) cases. On 24-locus MIRU-VNTR, clustering rate was 31%; the secondary case rate from a single primary source case was 20%.CONCLUSION: Africa in general, and the east-west pole of Africa in particular, harboured a genetically diverse population of MTBC, with characteristics of geographic segregation. Both generalist and specialist genotypes are circulating in the region. L4 is dominant across the continent, while M. bovis is rarely detected as a cause for human TB. The clinical significance of genetic diversity of MTBC in the different geographic and population groups of Africa is not fully understood. Both person-to-person transmission and reactivation mode of TB is significant in Africa. Prevention and control strategies should therefore envisage these two scenarios.