Schizoempodium mesophyllincola is an eriophyid mite that feeds in leaves of Populus trichocarpa in the central part of this cottonwood tree’s range (i.e., coastal British Columbia, Washington and Oregon) in the Pacific Northwest (PNW) of North America, and on some interspecific hybrids planted in short-rotation, intensive forestry in the region. The mite, a leaf vagrant, sucks the contents of spongy mesophyll cells, causing leaf discoloration, or “bronzing.” Here, we investigate the inheritance pattern of resistance to leaf bronzing using a three-generation Populus trichocarpa x P. deltoides hybrid pedigree. We found that resistance to the mite is an exaptation in that its source in two related F₂ families of the TxD hybrid pedigree was the non-native host, P. deltoides. Two grandparental genotypes of the latter, ‘ILL-5’ and ‘ILL-129’, were completely free of the bronzing symptom and that phenotype was inherited in a Mendelian manner in the F₁ and F₂. Resistance to S. mesophyllincola is similar to resistance to many other regional pathogens of P. trichocarpa (e.g., Melampsora occidentalis, Venturia inopina, Sphaerulina populicola, and Taphrina sp.) in that it is inherited from the non-native grandparent (e.g., P. deltoides, P. nigra, or P. maximowiczii) in three-generation, hybrid pedigrees. In addition to finding evidence for Mendelian inheritance, we found two QTLs with LOD scores 5.03 and 3.12 mapped on linkage groups (LG) III and I, and they explained 6.7 and 4.2% of the phenotypic variance, respectively. The LG I QTL is close to, or synonymous with, one for resistance to sap-feeding arthropods and leaf developmental traits as expressed in a British study utilizing the same pedigree.