The increasing trend of Escherichia coli producing extended-spectrum beta-lactamases (ESBLs) and carbapenemases is a global public health concern. In this study, prevalence and molecular characteristics of E. coli harboring ESBL and carbapenemase genes were investigated for 426 isolates derived from various clinical specimens in a teaching hospital in Yangon, Myanmar, for the 1-year period beginning January 2016. A total of 157 isolates (36.9%) were ESBL producers and harbored CTX-M-1 group genes (146 isolates; bla CTX-M-15 , bla CTX-M55 ) or CTX-M-9 group genes (11 isolates; bla CTX-M-14 , bla CTX-M-27 ). Carbapenem resistance was detected in 35 isolates (8.2%), among which 26 isolates had carbapenemase genes encoding NDM-1 (2 isolates), NDM-4 (6 isolates), NDM-5 (14 isolates), NDM-7 (3 isolates), and OXA-181 (2 isolates). bla NDM-5 was identified in phylogenetic groups A, B1, and D isolates belonging to various genotypes (ST101, ST354, ST405, ST410, ST1196) associated with bla TEM-1 , bla CTX-M-15 , bla OXA-181 , bla CMY-2 , bla CMY-6 , bla CMY-42 , qnrB , qnrS , or aac6′-Ib-cr . While two isolates with bla OXA-181 belonged to phylogenetic group A-ST410, one isolate had also bla NDM-5 , as well as bla CTX-M-15 and bla CMY-2 , and the other harbored bla CMY-42 and aac6′-Ib-cr , showing different resistance patterns. Phylogenetic group B2 isolates examined were classified into mostly ST131 and had solely bla CTX-M-15 or bla CTX-M-27 , harboring more virulence factors than other phylogenetic groups. The present study revealed high prevalence of ESBL genes represented by bla CTX-M-15 and dominance of bla NDM-5 among NDM genes, disseminating to various E. coli clones. Notably, carbapenemase gene encoding OXA-181 was first identified in Myanmar, suggesting its spread together with NDM genes.