Strategic spatial patterning of crop species and cultivars could make agricultural landscapes less vulnerable to plant disease epidemics, but experimentation to explore effective disease-suppressive landscape designs is problematic. Here, we present a realistic, multiscale, spatiotemporal, integrodifference equation model of potato late blight epidemics to determine the relationship between spatial heterogeneity and disease spread, and determine the effectiveness of mixing resistant and susceptible cultivars at different spatial scales under the influence of weather. The model framework comprised a landscape generator, a potato late blight model that includes host and pathogen life cycles and fungicide management at the field scale, and an atmospheric dispersion model that calculates spore dispersal at the landscape scale. Landscapes consisted of one or two distinct potato-growing regions (6.4-by-6.4-km) embedded within a nonhost matrix. The characteristics of fields and growing regions and the separation distance between two growing regions were investigated for their effects on disease incidence, measured as the proportion of fields with ≥1% severity, after inoculation of a single potato grid cell with a low initial level of disease. The most effective spatial strategies for suppressing disease spread in a region were those that reduced the acreage of potato or increased the proportion of a resistant potato cultivar. Clustering potato cultivation in some parts of a region, either by planting in large fields or clustering small fields, enhanced the spread within such a cluster while it delayed spread from one cluster to another; however, the net effect of clustering was an increase in disease at the landscape scale. The planting of mixtures of a resistant and susceptible cultivar was a consistently effective option for creating potato-growing regions that suppressed disease spread. It was more effective to mix susceptible and resistant cultivars within fields than plant some fields entirely with a susceptible cultivar and other fields with a resistant cultivar, at the same ratio of susceptible to resistant potato plants at the landscape level. Separation distances of at least 16 km were needed to completely prevent epidemic spread from one potato-growing region to another. Effects of spatial placement of resistant and susceptible potato cultivars depended strongly on meteorological conditions, indicating that landscape connectivity for the spread of plant disease depends on the particular coincidence between direction of spread, location of fields, distance between the fields, and survival of the spores depending on the weather. Therefore, in the simulation of (airborne) pathogen invasions, it is important to consider the large variability of atmospheric dispersion conditions.