Catheter-associated urinary tract infection (CAUTI) presents a significant health problem worldwide and is associated with increased morbidity and mortality. Herein, a silver-polytetrafluoroethylene (Ag-PTFE) nanocomposite coating for catheters was developed via a facile wet chemistry method. Benefiting from the synergistic effect of Ag and PTFE, the as-prepared Ag-PTFE-coated catheter exhibited enhanced antibacterial and antiadhesive activities against two CAUTI-associated strains: E. coli WT F1693 and S. aureus F1557. Compared to the uncoated commercial silicone catheters and the Ag-coated catheters, the Ag-PTFE-coated catheters were able to reduce bacterial adhesion by up to 60.3% and 55.2%, respectively. The Ag-PTFE-coated catheters also exhibited strong antibiofilm activity, reducing biofilm coverage by up to 97.4% compared with the commercial silicone catheters. In an in vitro bladder model, the Ag-PTFE-coated catheter displayed excellent anti-infection efficacy against bacteriuria, extending the lifetime of silicone catheters from a mean of 6 days to over 40 days. The Ag-PTFE coating also showed good biocompatibility with fibroblast cells in culture, making it a prospective strategy to overcome current challenges in CAUTI.