Background: Macrolides are considered one of the oldest classes of antibiotics which have been regarded among the best-tolerated antibiotic for almost several years. They are characterized by their large lactone ring structures and by their growth-inhibiting (bacteriostatic) effects on bacteria. Aim: The potency of macrolide antibiotics were determined against enteric bacteria (E. coli, Shigella spp. and Salmonella spp.) isolated during the raining season between June to September in the year 2018 from locations in Ado Ekiti metropolis. The consequences of the presence of these bacteria can be fatal hence the need to investigate their susceptibility to macrolide antibiotics. Methods: The bacteria were isolated from well water, soil and drainage samples obtained at Erifun, Omisanjana, Fiyinfoluwa, Ajilosun areas using serial dilution method. Results: It was observed that the bacteria were susceptible to 250 µg/mL and 500 µg/mL concentration of Azithromycin, Erythromycin, and Clarithromycin though with varying degrees of susceptibility. Azithromycin showed the highest potency. Conclusion: The present study indicated samples of the well water, soil and drainage at Erifun, Omisanjana, Ajilosun and Fiyinfoluwa areas of Ado-Ekiti were severely contaminated with E. coli, Salmonella spp., and Shigella spp. this is due to the lack of adequate sanitary measures. However, unhygienic behaviour like indiscriminate disposal of waste and open defecation should be discouraged.