Both theory and experimental evolution studies predict migration to influence the outcome of antagonistic coevolution between hosts and their parasites, with higher migration rates leading to increased diversity and evolutionary potential. Migration rates are expected to vary in spatially structured natural pathosystems, yet how spatial structure generates variation in coevolutionary trajectories across populations occupying the same landscape has not been tested. Here, we studied the effect of spatial connectivity on host evolutionary potential in a natural pathosystem characterized by a stable Plantago lanceolata host network and a highly dynamic Podosphaera plantaginis parasite metapopulation. We designed a large inoculation experiment to test resistance of five isolated and five well-connected host populations against sympatric and allopatric pathogen strains, over 4 years. Contrary to our expectations, we did not find consistently higher resistance against sympatric pathogen strains in the well-connected populations. Instead, host local adaptation varied considerably among populations and through time with greater fluctuations observed in the well-connected populations. Jointly, our results suggest that in populations where pathogens have successfully established, they have the upper hand in the coevolutionary arms race, but hosts may be better able to respond to pathogen-imposed selection in the well-connected than in the isolated populations. Hence, the ongoing and extensive fragmentation of natural habitats may increase vulnerability to diseases.