Ecological theory predicts that disease incidence increases with increasing density of host networks, yet evolutionary theory suggests that host resistance increases accordingly. To test the combined effects of ecological and evolutionary forces on host-pathogen systems, we analyzed the spatiotemporal dynamics of a plant (Plantago lanceolata)-fungal pathogen (Podosphaera plantaginis) relationship for 12 years in over 4000 host populations. Disease prevalence at the metapopulation level was low, with high annual pathogen extinction rates balanced by frequent (re-) colonizations. Highly connected host populations experienced less pathogen colonization and higher pathogen extinction rates than expected; a laboratory assay confirmed that this phenomenon was caused by higher levels of disease resistance in highly connected host populations.