Marine biofouling is a sticky global problem that hinders maritime industries. Various microscale surface structures inspired by marine biological species have been explored for their anti‐fouling properties. However, systematic studies of anti‐marine‐fouling performance on surface architectures with characteristic length‐scales spanning from below 100 nm to greater than 10 µm are generally lacking. Herein, a study on the rational design and fabrication of ZnO/Al2O3 core–shell nanowire architectures with tunable geometries (length, spacing, and branching) and surface chemistry is presented. The ability of the nanowires to significantly delay or prevent marine biofouling is demonstrated. Compared to planar surfaces, hydrophilic nanowires can reduce fouling coverage by up to ≈60% after 20 days. The fouling reduction mechanism is mainly due to two geometric effects: reduced effective settlement area and mechanical cell penetration. Additionally, superhydrophobic nanowires can completely prevent marine biofouling for up to 22 days. The nanowire surfaces are transparent across the visible spectrum, making them applicable to windows and oceanographic sensors. Through the rational control of surface nano‐architectures, the coupled relationships between wettability, transparency, and anti‐biofouling performance are identified. It is envisioned that the insights gained from the work can be used to systematically design surfaces that reduce marine biofouling in various industrial settings.