Aeromonas hydrophila is an opportunistic fish pathogen, significantly impacting aquaculture production worldwide. A total number of 150 mullets (Mugil cephalus) was collected to detect the presence of virulent Aer. hydrophila in fish farms suffering from mass mortality. In addition, the antibiotic-resistant genes were determined for the isolated strains, viz. tetracycline (TetA (A), sulphonamide (Sul1), and quinolones (qnrsA). The isolated strains were identified as Aer. hydrophila and were registered at NCBI under accession numbers (OM965641, OM965642 and OM965643). They prevailed at a rate of 96%, 92%, and 86% in the three sites under investigation. The isolated strains harbored virulence genes cytotonic enterotoxins heat-stable (ast) and cytotoxic enterotoxin (act). The isolated Aer. hydrophila had resistant genes for TetA(A), Sul1, qnrsA.  Therefore, this study was conducted to shed the light on a serious obstacle facing aquaculture. In addition, fish farmers should avoid the excessive and random antibiotic uses resulting in emerging antibiotic-resistant bacteria.