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Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed by the disk diffusion method. Antibiotic-resistance genes for class A beta-lactamases, carbapenemases, and plasmid resistance to colistin resistance (<i>mcr-1–8</i>) were screened by RT-PCR. (2) Results: The 240 enterobacteria were composed of: <i>Escherichia coli</i> (60.83%), <i>Klebsiella pneumoniae</i> (21.67%), <i>Enterobacter cloacae</i> (13.75%), <i>Citrobacter freundii</i> (2.08%), <i>Serratia marcescens</i> (0.83%), <i>Klebsiella aerogenes</i> (0.42%), and <i>Proteus mirabilis</i> (0.42%). Class A beta-lactamase genes were found in 229 isolates (70.41% <i>bla</i>_TEM, 37.5% <i>bla</i>_SHV, 83.75% <i>bla</i>_CTX-A, and 0.42% <i>bla</i>_CTX-B). The carbapenemase genes <i>bla</i>_OXA-48 and <i>bla</i>_NDM were found in 25 isolates, including 14 isolates with <i>bla</i>_OXA-48, 13 isolates with <i>bla</i>_NDM, and 2 isolates with both genes simultaneously. The <i>mcr-8</i> gene was found in one isolate of <i>E. cloacae</i>. (3) Conclusions: The epidemiology of antibiotic-resistance genes in enterobacteria in Senegal shows the emergence of CPEs. This phenomenon is worrying, and rigorous surveillance is necessary to avoid further spread.