In what is a major threat to global public health security, the rapid development of antimicrobial resistance (AMR) means that many bacteria have developed resistance to multiple antimicrobial agents, including the last-line drug polymyxin. Hence, there is an urgent need to develop new drugs and therapies to address the persistent rise of polymyxin resistance. Bacteriophages (phages) are recognized both as alternative treatments and also as adjuvants that can revive bacterial susceptibility to antibiotics. In this study, a contractile phage specifically targeting Pseudomonas aeruginosa was isolated from wastewater in a general hospital. Screened against a panel of clinically diverse bacterial strains, this phage named vB3530 was able to lyse 13 out of 16 clinical isolates of Pseudomonas aeruginosa. Genome sequencing and transmission electron microscopy (TEM) analyses revealed that vB3530 belongs to the Pbunavirus family of viruses. In classic checkerboard assays, we found that phage vB3530 effectively restored the susceptibility of resistant bacteria to polymyxin, leading to a 1024-fold reduction in the minimum inhibitory concentration (MIC) of polymyxin. In initial work to understand the mechanism of the phage activity, we isolated a series of phage-resistant mutant strains that exhibited significantly reduced growth capacity, with smaller and more transparent colony morphologies. Their MIC for polymyxin, decreased from 256 μg/mL to 0.5 μg/mL. Whole-genome comparisons of the parental and phage-resistant strains showed that mutations providing phage-resistance occurred in the LPS synthesis gene GalU and the O-antigen chain length gene Wzz. Our findings indicate that Pseudomonas aeruginosa employs various strategies, including mutations that modify LPS structure, to overcome phage infection. Concomitantly, these mutations enhance bacterial sensitivity to polymyxin and would benefit clinical treatment. Our future work will address how leveraging phage induction in phage therapy may provide better information for clinical decisions regarding phage-antibiotic combinations.