Healthcare in low- and middle-income countries is becoming problematic due to the emergence of multidrug-resistant bacteria causing serious morbidity and mortality. Klebsiella variicola carrying multiple antimicrobial resistance (AMR) genes were found significantly among sepsis patients in a study done between October 2019 and September 2020 at four Ethiopian hospitals located in the central (Tikur Anbessa and Yekatit 12), southern (Hawassa), and northern (Dessie) parts. Among 1416 sepsis patients, 74 K. variicola isolates were identified using MALDI-TOF, most of them at Dessie (n = 44) and Hawassa (n = 28) hospitals. Whole genome sequencing showed that K. variicola strains identified at Dessie Hospital displayed phylogenetic clonality, carried an IncM1 plasmid and the majority were ST3924. Many K. variicola identified at Hawassa Hospital were clonally clustered and the majority belonged to novel STs and carried IncFIB(K) and IncFII(K) plasmids concurrently. Fifty K. variicola carried ESBL genes while 2 isolates harboured AmpC. Other frequently found genes were aac(3)-lla, bla_CTX-M-15, bla_TEM-1B, bla_LEN2, bla_OXA-1, bla_SCO-1, catB3, dfrA14, QnrB1, aac(6’)-lb-cr and sul2. Virulence genes detected at both sites were mrk operons for biofilm formation and siderophore ABC transporter operons for iron uptake. Capsular alleles varied, with wzi 269 at Dessie and wzi 582 at Hawassa. The isolation of multidrug-resistant K. variicola as an emerging sepsis pathogen calls for strong infection prevention strategies and antimicrobial stewardship supported by advanced bacterial identification techniques.