Synthetic controls of crop pathogens are increasingly associated with harm to the environment and human health, and pathogen resistance. Pesticide residues in crops can also act as non-tariff trade barriers. There is therefore a strong imperative to develop biologically based and natural product (NP) biofungicides as more sustainable alternatives for crop pathogen control. We demonstrate the field efficacy, over multiple seasons, of NP biofungicides, NP1 (based on anhydrous milk fat) and NP2 (based on soybean oil), on two major diseases of winegrapes—Botrytis bunch rot (Botrytis) and powdery mildew (PM). The NPs were integrated into a season-long integrated disease management programme that has produced chemical-residue-free wines. Efficacies for Botrytis control on three different varieties were: 63–97% on Chardonnay, 0–96% for Sauvignon Blanc and 46–58% on Riesling; with 65–98% PM control on Chardonnay and Riesling. NP2 exhibited the significant control of Botrytis latent infections, making it a viable alternative to mid-season synthetic fungicides. Disease control was significantly better than the untreated control and usually as efficacious as the synthetic fungicide treatment(s). Yields and wine quality in NP-treated crops were normally equivalent to those in the synthetic fungicide treatments. The results indicate that NP-mediated disease control of Botrytis and powdery mildew can be obtained in the vineyard, without synthetic fungicide input.