Edwardsiella ictaluri is an emerging bacterial pathogen that affects farmed tilapia ( Oreochromis spp.). This study reports the arrival, establishment, and widespread findings 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 seeds, while outbreaks in seven farms were from domestic sources. Clinically sick fish showed the appearance of numerous white spots in visceral organs, and accumulative mortality reached 30%–65%. Twenty-six representative bacterial isolates recovered from 26 disease outbreaks were identified as E. ictaluri based on a combination of phenotypic tests, genus- and species-specific polymerase chain reaction assays, 16S rRNA and gyrB sequencing, and phylogenetic analysis. All isolates harbored the same virulence gene profiles esrC ⁺, evpC ⁺, ureA-C ⁺, eseI^-, escD^-, and virD4^-. Antimicrobial susceptibility tests revealed that 80.8%–100% of isolates were multidrug resistant, with resistance to 4–8 antimicrobials in the groups of penicillin, macrolides, sulfonamides, amphenicols, and glycopeptides. The experimental challenge successfully induced disease that mimicked natural infection. The median lethal doses (LD ₅₀) of the tested isolates (n = 4) were 42–61 colony forming units/fish, indicating their extremely high virulence. This emerging pathogen is established and has spread to various geographical locations, causing serious impacts on farmed tilapia in northern Vietnam. It is likely that this pathogen will continue to spread through contaminated stocks (both imported and domestic sources) and persist. Thus, increased awareness, combined with biosecurity measures and emergent vaccination programs is essential to mitigate the negative impact of this emerging disease on the tilapia farming industry.