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The most widely distributed <i>bla</i>_CTX-M gene on a global scale is <i>bla</i>_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 <i>bla</i>_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 <i>bla</i>_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including IS<i>Ecp1,</i> IS<i>26,</i> orf<i>447,</i> IS<i>903,</i> and IS<i>3</i> have been detected which are associated with the genetic environment of <i>bla</i>_CTX-M-15 in Africa. Seven different genetic patterns were seen in the <i>bla</i>_CTX-M-15 genetic environment. Insertion sequence IS<i>Ecp1</i> was commonly located upstream of the end of the <i>bla</i>_CTX-M-15 gene, while the insertion sequence orf<i>477</i> was located downstream. In some studies, IS<i>Ecp1</i> was truncated upstream of <i>bla</i>_CTX-M-15 by insertion sequences IS<i>26</i> and IS<i>3</i>. The class 1 integron (<i>Intl1</i>) was most commonly reported to be associated with <i>bla</i>_CTX-M-15 (13 studies), with <i>Intl1/dfrA17–aadA5</i> 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 <i>bla</i>_CTX-M-15 gene. Aminoglycoside-modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with the <i>bla</i>_CTX-M-15 gene on plasmids. This review revealed the predominant role of IS<i>Ecp1</i>, <i>Intl1</i> and IncF plasmids in the mobilization and continental dissemination of the <i>bla</i>_CTX-M-15 gene in Africa.