Amphiphilic methacrylate copolymers (Si-co-EF) containing polysiloxane (Si) and mixed poly(oxyethylene)-perfluorohexyl (EF) side chains were synthesized with different compositions and used together with polysiloxane-functionalized nanoparticles as additives of condensation cured nanocomposite poly(siloxane) films. The mechanical properties of the nanocomposite films were consistent with the elastomeric behavior of the poly(siloxane) matrix without significant detriment from either the copolymer or the nanoparticles. Films were found to be markedly hydrophobic and liphophobic, with both properties being maximized at an intermediate content of EF units. The high enrichment in fluorine at the film surface was proven by angle-resolved X-ray photoelectron spectroscopy (AR-XPS). Long-term marine antifouling performance was evaluated in field immersion trials of test panels for up to 10 months of immersion. Both nanoparticles and amphiphilic copolymer were found to be highly effective in reducing the colonization of foulants, especially hard macrofoulants, when compared with control panels. Lowest percentage of surface coverage was 20% after 10 months of immersion (films with 4 wt% copolymer and 0.5 wt% nanoparticles), which was further decreased to less than 10% after exposure to a water jet for 10 s. The enhanced antifouling properties of coatings containing both nanoparticles and copolymer were confirmed by laboratory assays against the polychaete Ficopomatus enigmaticus and the diatom Navicula salinicola.