The global rise in antibiotic-resistant bacterial infections necessitates innovative strategies beyond conventional antibiotics. Phage-derived depolymerases selectively degrade bacterial capsules and biofilms, weakening pathogen defenses and enhancing immune clearance. This approach offers a highly specific and resistance-sparing intervention. Our study aims to determine whether phage depolymerases can enhance the efficacy of phage therapy, potentially serving as a novel anti-virulence strategy for bacterial infections. A panel of seven lytic Acinetobacter baumannii phages, isolated from local sewage samples, and six recombinant depolymerases were employed. The effects of depolymerases on each phage's host range and bacterial growth inhibition were assessed using spot-testing assays and bacterial growth curves. Synergy assays demonstrated that combining varying concentrations (0.8–50 ng/mL) of depolymerases with 10²–10⁸ PFU/mL of phage significantly inhibited the growth of several A. baumannii strains. This combination outperformed high doses of either phage or depolymerase alone, as shown by area under the curve analysis, achieving up to 85% growth inhibition compared to the controls. Notably, certain phage–depolymerase combinations led to a remarkable six-log increase in the phage endpoint titer. Efficiency of plating studies further showed that depolymerases expanded the phage host range, enabling broader therapeutic applications without the need for phage adaptation or engineering. To our knowledge, this is the first study to show that phage depolymerases enhance both the efficacy and host range of therapeutic phages. The promises and challenges of exploring phage depolymerases as a strategy to combat antimicrobial resistance, particularly against bacteria that produce protective capsules or biofilms, will be discussed.