Background: The success of phage therapy is affected by the method of treatment delivery. This study focused on comparing different phage delivery routes, specifically oral (phage-impregnated feed), intraperitoneal (IP), and bath (immersion), in treatment of induced motile Aeromonas septicemia (MAS). Materials and Methods: The efficacy of Aeromonas hydrophila phage cocktail in treating MAS-infected Oreochromis niloticus through different delivery routes was assessed by challenging the fish with 100% lethal dose of A. hydrophila and conducting a 15-day treatment regimen. Blood and kidney samples were analyzed for bacterial and phage concentrations. Results: All routes exhibited reduction of disease symptoms, significant ( p < 0.05) decrease in bacterial count, and increase in phage count. Notably, IP route showed significant activity in reducing bacterial load. Conclusions: Phage therapy through IP route is the most effective yet invasive in controlling MAS infection in O. niloticus. The efficacy of oral route depends on the fish's intake of feeds, whereas the bath route was the least effective.