This communication reports strongly anisotropic wetting behavior on one-dimensional nanopatterned surfaces. Contact angles, degree of anisotropy, and droplet distortion are measured on micro- and nanopatterned surfaces fabricated with interference lithography. Both the degree of anisotropy and the droplet distortion are extremely high as compared with previous reports because of the well-defined nanostructural morphology. The surface is manipulated to tune with the wetting from hydrophobic to hydrophilic while retaining the structural wetting anisotropy with a simple silica nanoparticle overcoat. The wetting mechanisms are discussed. Potential applications in microfluidic devices and evaporation-induced pattern formation are demonstrated.