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; blaCTX-M-15, blaCTX-M55) or CTX-M-9 group genes (11 isolates; blaCTX-M-14, blaCTX-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). blaNDM-5 was identified in phylogenetic groups A, B1, and D isolates belonging to various genotypes (ST101, ST354, ST405, ST410, ST1196) associated with blaTEM-1, blaCTX-M-15, blaOXA-181, blaCMY-2, blaCMY-6, blaCMY-42, qnrB, qnrS, or aac6'-Ib-cr. While two isolates with blaOXA-181 belonged to phylogenetic group A-ST410, one isolate had also blaNDM-5, as well as blaCTX-M-15 and blaCMY-2, and the other harbored blaCMY-42 and aac6'-Ib-cr, showing different resistance patterns. Phylogenetic group B2 isolates examined were classified into mostly ST131 and had solely blaCTX-M-15 or blaCTX-M-27, harboring more virulence factors than other phylogenetic groups. The present study revealed high prevalence of ESBL genes represented by blaCTX-M-15 and dominance of blaNDM-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.