Edwardsiella tarda (E. tarda) is a zoonotic bacterium that causes edwardsiellosis, characterized by extensive mortality in fish leading to high economic losses, little information is available on the molecular characterization of antimicrobial resistance in E. tarda. Therefore, the objective of this research was to depict at the molecular level, E. tarda's antimicrobial resistance isolated from tilapia fish in Egypt which was identified by both biochemical tests (Microbact™) and PCR using species specific primers targeting the gyrase B1( gyrB1)gene (a taxonomic marker for E. tarda) at 415 bp. Twenty-four E. tarda isolates were isolated from 100 diseased fish samples randomly collected from 10 private fish farms (ten fish each) in the Kafr El-Sheikh governorate, Egypt. The susceptibility of all isolates was determined against 10 antimicrobial agents (amoxicillin (AMX), ampicillin (AMP), ciprofloxacin (CIP), tetracycline (TE), cefotaxime (CTX), streptomycin (S), erythromycin (E), norfloxacin, amoxicillin/Clavulanic acid, and sulbactam/ampicillin) as most of these isolates demonstrate multidrug resistant phenotypes as the complete resistance were against erythromycin (100%) then the highest resistance against tetracycline and amoxicillin (83.3%). Antibiotic resistance genes were screened and characterized using PCR. β-Lactamase-encoding genes have been discovered as follows: blaTEM and blaSHV in 85.7% and 14.2% isolate, respectively. While blaOXA and blaCTX-M were not detected, tetracycline resistance genes were identified as follows: tetA in 57.1% and tetB in 42.8%, but the erythromycin resistance gene (ermB) was not detected. This study demonstrated that fish are potential sources of multidrug-resistant E. tarda.