We characterized five carbapenemase-producing <i>Enterobacterales</i> (CPE) isolates from two health care institutions in Lima, Peru. The isolates were identified as Klebsiella pneumoniae (<i>n</i> = 3), Citrobacter portucalensis (<i>n</i> = 1), and Escherichia coli (<i>n</i> = 1). All were identified as <i>bla</i>_OXA-48-like gene carriers using conventional PCR. Whole-genome sequencing found the presence of the <i>bla</i>_OXA-181 gene as the only carbapenemase gene in all isolates. Genes associated with resistance to aminoglycosides, quinolones, amphenicols, fosfomycins, macrolides, tetracyclines, sulfonamides, and trimethoprim were also found. The plasmid incompatibility group IncX3 was identified in all genomes in a truncated Tn<i>6361</i> transposon flanked by ΔIS<i>26</i> insertion sequences. The <i>qnrS1</i> gene was also found downstream of <i>bla</i>_OXA-181, conferring fluoroquinolone resistance to all isolates. CPE isolates harboring <i>bla</i>_OXA-like genes are an increasing public health problem in health care settings worldwide. The IncX3 plasmid is involved in the worldwide dissemination of <i>bla</i>_OXA-181, and its presence in these CPE isolates suggests the wide dissemination of <i>bla</i>_OXA-181 in Peru. <b>IMPORTANCE</b> Reports of carbapenemase-producing <i>Enterobacterales</i> (CPE) isolates are increasing worldwide. Accurate detection of the β-lactamase OXA-181 (a variant of OXA-48) is important to initiate therapy and preventive measures in the clinic. OXA-181 has been described in CPE isolates in many countries, often associated with nosocomial outbreaks. However, the circulation of this carbapenemase has yet to be reported in Peru. Here, we report the detection of five multidrug-resistant CPE clinical isolates harboring <i>bla</i>_OXA-181 in the IncX3-type plasmid, a potential driver of dissemination in Peru.