Several species of plants and animals demonstrate an ability to resist the accumulation of contaminants natural to their environments. To explain this phenomenon, mechanisms that facilitate fouling resistance must be deciphered. Along these lines, this study is focused on the topography-based mechanisms observed in nature that represent one of several mechanisms employed by nature for underwater environments. The prevailing theory for the fouling resistant performance of sharkskin is that a positive correlation exists with its ability to reduce skin friction drag relative to what is expected for a flat surface. This correlation was investigated for three novel topographies inspired by sharkskin, fish-scales, and mollusks. Numerical simulations involving Large Eddy Simulation with the Wall Adapting Local Eddy-Viscosity model were carried out for turbulent flow conditions to determine the most effective dimensions of the three topographies for drag reduction. The maximum drag reduction attained in this study was 6.0%, 6.7%, and 6.1% for the bioinspired sharkskin, fish-scales, and mollusk surfaces. A flow field analysis revealed that each surface exhibited a reduction in turbulent velocity fluctuations near the surface. Following this, functional samples were fabricated in acrylic by means of a multi-axis machining center. Surface quality and form accuracy of the fabricated samples were assessed with an optical microscope and optical profilometer. Finally, a field study was conducted to investigate the fouling resistance of the samples by subjecting them to a flow of contaminated water for a period of 20 days. The flow conditions and characteristic dimensions of the geometry were chosen beforehand such that a subset of the samples was operating at drag reducing conditions, while the second subset was operating at drag increasing conditions. The results demonstrate for the first time that drag reduction is positively correlated with fouling resistance. The primary mechanism for this performance was identified as a decrease in inertial impaction of the fouling constituents as a consequence of the reduced turbulent velocity fluctuations.