Co-infections by multiple pathogen strains are common in the wild. Theory predicts co-infections to have major consequences for both within- and between-host disease dynamics, but data are currently scarce. Here, we study co-infection dynamics of powdery mildew Podosphaera plantaginis in its host populations of Plantago lanceolata in the Åland Islands, SW Finland. We find coinfection to be common yet spatially structured in the wild. A common garden experiment showed that disease prevalence was higher in co-infected treatments both at the host genotype and population levels than in singly-infected treatments. Our experimental findings are confirmed in natural pathogen populations—more devastating epidemics were measured in populations with higher levels of co-infection. Moreover, populations supporting high levels of co-infection had higher pathogen survival between seasons, and genetic diversity is increased suggesting increased opportunities for outcrossing in the pathogen. Jointly, our results confirm the predictions made by theoretical and experimental studies for the potential of co-infection to alter disease dynamics across a large host–pathogen metapopulation.