Edwardsiella ictaluri is an emerging bacterial pathogen affecting farmed tilapia ( Oreochromis spp.). This study reports the arrival, establishment and widespread of E. ictaluri in farmed tilapia in Vietnam. Among 26 disease outbreaks from 9 provinces in Northern Vietnam during 2019-2021, 19 outbreaks originated from imported stocked seeds while outbreaks in 7 farms were from domestic sources. Clinically sick fish showed appearance of numerous white spots in visceral organs, and accumulative mortalities reached 30-65%. Twenty-six representative bacterial isolates recovered from 26 disease outbreaks were then identified as E. ictaluri based on a combination of phenotypic tests, genus- and species-specific PCR assays, 16S rRNA and gyrB sequencing and phylogenetic analysis. All isolates harbored the same virulence gene profile esrC ⁺, evpC ⁺, ureA-C ⁺, eseI^-, escD^- and virD4^-. Antimicrobial susceptibility tests revealed 80.8-100% isolates were multidrug-resistant, with resistance to 4-8 antimicrobials in the groups of penicillin, macrolide, sulfonamide, amphenicols, and glycopeptide. Experimental challenge successfully induced disease that mimicked natural infection. The median lethal dose (LD ₅₀) of the tested isolates (n = 4) were 42 to 61 CFU/fish, indicating their extremely high virulence. This emerging pathogen has already been established and spread to various geographical locations and causing serious impact to farmed tilapia in Northern Vietnam. It is likely that this pathogen will continue to occur through possibly contaminated stocks (both imported and domestic sources) and persist spreading. Thus, increased awareness combined with biosecurity measures and emergent vaccination programs are essential to mitigate the negative impact of this emerging disease on the tilapia farming industry.