Edwardsiella tardais one of the most significant fish pathogens, causes edwardsiellosis in a variety of freshwater fish species, and its antibiotic resistance against multiple drugs has made it a health risk worldwide. In this study, we aimed to investigate the antibiotic resistance (ABR) genes ofE. tardaand establish its antibiotic susceptibility. Thus, 540 fish (299Oreochromis niloticus, 138O.mossambicus, and 103O. aureus) were collected randomly from twelve fish farms in three districts of Punjab in Pakistan.E. tardawas recovered from 147 fish showing symptoms of exophthalmia, hemorrhages, skin depigmentation, ascites, and bacteria-filled nodules in enlarged liver and kidney. Antimicrobial susceptibility testing proved chloramphenicol, ciprofloxacin, and streptomycin effective, but amoxicillin, erythromycin, and flumequine ineffective in controlling edwardsiellosis. Maximum occurrence of qnrA, blaTEM, and sul3 genes ofE. tardawas detected in 45% in the liver, 58%, and 42% respectively in the intestine; 46.5%, 67.2%, and 55.9% respectively inO. niloticus; 24%, 36%, and 23% respectively in summer with respect to fish organs, species, and season, respectively. Motility, H2S, indole, methyl red, and glucose tests gave positive results. Overall,E. tardainfected 27.2% of fish, which ultimately caused 7.69% mortality. The Chi-squared test of independence showed a significant difference in the occurrence of ABR genes ofE. tardawith respect to sampling sites. In conclusion, the misuse of antibacterial agents has led to the emergence of ABR genes inE. tarda, which in association with high temperatures cause multiple abnormalities in infected fish and ultimately resulting in massive mortality.