Intensive use of antimicrobial agents in aquaculture provides a selective pressure creating reservoirs of drug-resistant bacteria and transferable resistance genes in fish pathogens and other bacteria in the aquatic environment. From these reservoirs, resistance genes may disseminate by horizontal gene transfer and reach human pathogens, or drug-resistant pathogens from the aquatic environment may reach humans directly. This study aims at identifying the antibiotic sensitivity patterns of Pseudomonas aeruginosa, Salmonella typhi, and Escherichia coli isolates from fish ponds in two localities (Ashiaman and Dawhenya) in the Greater Accra region of Ghana. A total of 43 isolates were tested using the KirbyBauer agar disc diffusion method against Ciprofloxacin (5 µg), Erythromycin (15 µg), Cefuroxime (30 µg), Gentamicin (10 µg), and Tetracycline (30 µg).P. aeruginosa was the most isolated organism with 90% prevalence, followed by E. coli (75%) and S. typhi (50%). All the P. aeruginosa isolates were resistant to Erythromycin and Cefuroxime while 90% of the S. typhi isolates were resistant to Tetracycline and Erythromycin. E. coli isolates showed 100, 93.33 and 66.66% resistance to Erythromycin, Cefuroxime and Tetracycline respectively. Gentamicin, Tetracycline and Ciprofloxacin were sensitive to 66.66, 61.10 and 50% of P. aeruginosa isolates respectively. Ciprofloxacin was sensitive to 90% of the S. typhi isolates whiles Gentamicin was sensitive to 70% of the S. typhi isolates. Ciprofloxacin and Gentamicin were more sensitive to E. coli isolates (80 and 66.66% sensitivity respectively). Multi-drug resistant strains were obtained in 77.78% of P. aeruginosa and 70% of S. typhi isolates whiles 66.67% of E. coli isolates were also resistant to more than two classes of the antibiotics tested. High levels of microbial resistance were observed in the isolates with 72.09% of isolates being multidrug resistant strains.