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Biodiversity plays multifaceted roles in societal development and ecological sustainability. In agricultural ecosystems, using biodiversity to mitigate plant diseases has received renewed attention in recent years but our knowledge of the best ways of using biodiversity to control plant diseases is still incomplete. In term of in-crop diversification, it is not clear how genetic diversity per se in host populations interacts with identifiable resistance and other functional traits of component genotypes to mitigate disease epidemics and what is the best way of structuring mixture populations. In this study, we created a series of host populations by mixing different numbers of potato varieties showing different late blight resistance levels in different proportions. The amount of naturally occurring late blight disease in the mixture populations was recorded weekly during the potato growing seasons. The percentage of disease reduction (PDR) in the mixture populations was calculated by comparing their observed late blight levels relative to that expected when they were planted in pure stands. We found that PDR in the mixtures increased as the number of varieties and the difference in host resistance (DHR) between the component varieties increased. However, the level of host resistance in the potato varieties had little impact on PDR. In mixtures involving two varieties, the optimum proportion of component varieties for the best PDR depended on their DHR, with an increasing skewness to one of the component varieties as the DHR between the component varieties increased. These results indicate that mixing crop varieties can significantly reduce disease epidemics in the field. To achieve the best disease mitigation, growers should include as many varieties as possible in mixtures or, if only two component mixtures are possible, increase DHR among the component varieties.