Pathogens are often the main selective agents acting in plant communities, thereby influencing the distribution of polymorphism at loci affecting resistance within and among natural plant populations. In addition, the outcome of plant-pathogen interactions can be drastically affected by abiotic and biotic factors at different spatial and temporal grains. The characterization of the adaptive genetic architecture of disease resistance in native heterogeneous environments is however still missing. In this study, we conducted an in situ Genome-Wide Association study in the spatially heterogeneous native habitat of a highly genetically polymorphic local mapping population of Arabidopsis thaliana, to unravel the adaptive genetic architecture of quantitative disease resistance. Disease resistance largely differed among three native soils and was affected by the presence of the grass Poa annua. The observation of strong crossing reactions norms among the 195 A. thaliana genotypes for disease resistance among micro-habitats, combined with a negative fecundity-disease resistance relationship in each micro-habitat, suggest that alternative local genotypes of A. thaliana are favored under contrasting environmental conditions at the scale of few meters. A complex genetic architecture was detected for disease resistance and fecundity. However, only few QTLs were common between these two traits. Heterogeneous selection in this local population should therefore promote the maintenance of polymorphism at only few candidate resistance genes.