The most widely distributed bla_CTX-M gene on a global scale is bla_CTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. The objective of this review was to describe the genetic environments of the bla_CTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was performed through PubMed, AJOL, and Google Scholar electronic databases; 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of bla_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected which are associated with the genetic environment of bla_CTX-M-15 in Africa. Seven different genetic patterns were seen in the bla_CTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the bla_CTX-M-15 gene, while the insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of bla_CTX-M-15 by insertion sequences IS26 and IS3. The class 1 integron (Intl1) was most commonly reported to be associated with bla_CTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transferred the bla_CTX-M-15 gene. Aminoglycoside-modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with the bla_CTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1 and IncF plasmids in the mobilization and continental dissemination of the bla_CTX-M-15 gene in Africa.