This study proposes a way to control the wettability of zinc oxide nanowires (NWs) by properly selecting the kind of seed layer used to promote the growth of the wires. ZnO seed layers were synthesized on silicon and conductive substrates by a physical vapor deposition approach and a wet-chemical route, namely, the radio frequency magnetron sputtering and the spin-coating techniques, respectively. ZnO NWs were grown by a hydrothermal method on each kind of seed layer and the results were compared. The morphologies and crystallographic orientations of the seed layers and the resulting NWs were investigated with the aim of correlating the characteristics of the underlying seed layer to those of the resulting NWs. Additional insights were obtained by performing optical contact angle (OCA) measurements on ZnO seed layers to study their wettability behavior immediately after the synthesis processes and two weeks later. Hydrophilic behavior was observed in both sputtered and spin-coated fresh seed layers. After two weeks of aging, a change in the wettability and a net transition from hydrophilic to hydrophobic behavior was observed in sputtered seed layers, whereas in the spin-coated films this transition was not so pronounced and was found to be dependent on the precursor concentration. OCA measurements carried out on ZnO NWs showed that the wettability of the NWs is strictly related to the nature of the underlying seed layers and does not depend on the aging time, in contrast to the behavior of the seed layers. Depending on the deposition method, we therefore obtained either highly hydrophilic or superhydrophobic nanowires, which demonstrates the possibility to strongly control the final wetting behavior of these nanostructures for the desired application, such as self-cleaning surfaces, antireflection coatings, or substrates to anchor biofunctional agents.