The green peach aphid (GPA; Myzus persicae Sülzer) is a damaging pest that has a broad host range that includes plants in the Brassicaceae, Solanaceae, Cucurbitaceae, and Rosaceae families. It also vectors several important viral diseases. However, how plants perceive GPA to limit infestation is poorly understood. This study demonstrates an important role for the HOMOLOG OF RPW8 4 (HR4), which encodes a protein that contains the RESISTANCE TO POWDERY MILDEW 8 (RPW8) motif that is found in some intracellular receptor proteins that are involved in defense against pathogens. In the accession Moscow of Arabidopsis thaliana, a Brassicaceae family plant, located at the RPW8 locus on chromosome 3 are RPW8.1 and RPW8.2, which confer resistance against a broad spectrum of powdery mildew pathogens. In comparison, in the powdery mildew-susceptible accession Columbia (Col-0), RPW8.1 and RPW8.2 are replaced by the homologous HR4Col-0. HR4Col-0, but not its homologs, was found to be involved in limiting GPA infestation. The presence of HR4Col-0 adversely impacted GPA fecundity, feeding from the phloem, and host selection. Transcriptomic analysis revealed that HR4Col-0 influences biological processes such as response to chitin, amino acid metabolism, and lipid metabolism. The resistance-enhancement ability of HR4Col-0 towards GPA infestation could be transferred to the Arabidopsis accession Wassilewskija and the oil-seed crop Camelina sativa, both of which naturally lack HR4. These findings position HR4Col-0 as a promising candidate for enhancing resistance to the GPA in plants other than Arabidopsis. This research significantly advances our understanding of plant immune mechanisms against an important agricultural pest.