Biomaterial-associated infections caused by bacterial contamination and the subsequent formation of biofilms on the surfaces are challenges faced by our healthcare system. In this work, povidone-iodine-functionalized fluorinated copolymers with stable antibacterial, antibiofilm, and antifouling activities were designed and prepared by a two-step synthesis. First, a series of poly(hexafluorobutyl methacrylate-co-N-vinyl-2-pyrrolidone), i.e., P(HFBMA-NVP), were synthesized by radical copolymerization at different feed ratios to acquire water insoluble and antifouling copolymers. At the second step, the NVP segments in the copolymer were complexed with iodine to obtain the objective antibacterial and antifouling copolymer P(HFBMA-NVP)-I. The chemical and physical characteristics of the copolymers were investigated using 1H NMR, FTIR, XPS, EDX, UV-Vis, SEM, TEM, elemental analysis, and contact angle measurement. P(HFBMA-NVP)-I exhibited excellent antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus), as well as good biocompatibility towards human hepatocyte cells (L02) and Caenorhabditis elegans. Using the electrospinning or spraying technique, P(HFBMA-NVP)-I was coated on polystyrene slides, medical stainless steel sheets, and cotton fabric, allowing the surfaces to have stable antibacterial and antibiofilm activities against pathogenic bacteria and antifouling capability against foulants and blood, and exhibit excellent self-cleaning properties.