The vine is highly susceptible to numerous fungal diseases, the incidence and severity of which are increasing because of climate change. To fight them, large amounts of phytosanitary products are generally used, although they entail important economic and environmental costs. The new fungus resistant vine varieties (PIWI) constitute one of the most active lines of research on plant material in viticulture and are regarded as a viable solution to respond to the requirements of European Directive 2009/128/EC. In the present work, the evolution and impact of the three main fungal diseases (powdery mildew, downy mildew and botrytis bunch rot) were monitored in plots in the Somontano region (Huesca, Spain), comparing three PIWI varieties (Sauvignon Kretos, Souvignier gris and Muscaris) with a susceptible control variety (Sauvignon blanc) in real field growing conditions over three successive years (2016–2018). The main ampelographic characters of each variety were studied and a weekly follow-up was carried out to track the development of each disease, relating it to climatic variables. Regardless of the climatic conditions (one of the growing seasons was rainy and the other two corresponded to dry years, with differences in the distribution of rainfall), the three PIWI varieties hardly presented any symptoms, demonstrating a high resistance to downy mildew and powdery mildew and even to botrytis. Principal component analysis results pointed to a differential behavior versus the control and treated Sauvignon blanc plants in terms of disease resistance. Based on production results, despite the youth of the plantation, the excellent potential of Sauvignon Kretos variety was observed. However, from the analysis of the quality of wine obtained in microvinifications from these fungus resistant varieties in the second and third year, the one obtained from Muscaris seemed to have the best organoleptic properties. Apart from environmental considerations, given that these fungus resistant varieties can significantly contribute to the sustainability of wineries, they may also respond to the demand of consumers who want zero-pesticide products or of the supporters of ecological products adjusted to European regulations.