<p><i>Klebsiella pneumoniae</i> (<i>K. pneumoniae</i>) is one of the notorious pathogens with rapidly evolving antimicrobial resistance (AMR) globally. With an unpredictable trend of AMR, colistin is the last resort antibiotic, but its resistance pattern in sub-Saharan Africa is comparatively unknown, hampering the prediction of international transmission. Here, we aimed to dissect a comparative AMR among strains isolated from Tanzania, Kenya, Uganda, and Ethiopia and to obtain a snapshot of versatility in colistin resistance. We retrieved whole genome sequence datasets and performed single nucleotide polymorphism (SNP) analysis along with comparative AMR analysis using ResFinder and Comprehensive Antibiotic Resistance Database (CARD to obtain genes and mutations related to AMR. Further, we performed Multilocus sequence typing (MLST) to unveil lineages and plasmids critical for AMR. Our results uncovered widespread resistance to fluoroquinolones, β-lactams, and aminoglycosides with diverse plasmid-mediated resistance mechanisms. Colistin resistance is largely determined by nonsynonymous SNPs of genes <i>arn, pmrA/B, pagP,</i> and <i>eptA/B</i> across the countries. Importantly, we found two Kenyan strains carrying the <i>mcr-8.1</i> gene conferring colistin resistance. All the countries possess MDR strains, with Kenya emerging as the leading and the only country harboring <i>mcr</i> genes so far. The detection of chromosomal and plasmid-borne colistin resistance, including <i>mcr-8.</i>1 on IncR plasmids, underscores a critical threat to last-line antibiotics. Taken together, our findings underscore a potential risk of the evolution of colistin-resistant <i>K. pneumoniae</i> strains with resistance mechanisms integrating mcr and chromosomal lipid A-modifying enzymes, highlighting the urgent need for surveillance and antimicrobial stewardship revisits across the region.</p>