We investigate the effects of vacancy defects on the electronic and magnetic properties of zigzag graphene nanoribbons (zGNRs) by making use of the Green’s function formalism in combination with a tight-binding Hamiltonian. We explain the evolution of indirect exchange coupling, known as the Ruderman–Kittel–Kasuya–Yosida (RKKY) interaction, including single, double, and multiple 5-8-5 divacancy (DV) defects. Our numerical calculations show that changes in the electronic structure and exchange coupling of zGNRs depend to a significant degree on the location of DV defects with respect to the ribbon edges and the number of DV defects. In the case where both impurities are located on the edge, the magnitude of the exchange coupling is several orders of magnitude higher than when they are placed on the interior of the nanoribbon. Furthermore, a periodic DV causes a dramatic change in the magnetic ground state of the ribbon. In the limit of a high vacancy potential, the strength of the RKKY interaction is approximately independent of the Fermi energy. We demonstrate that, on the one hand, the defect engineering of atomic vacancies is a promising way to modify the magnetic properties of graphene nanoribbons, and, on the other hand, unusual RKKY oscillations around the DVs are a new technique for directly probing the local vacancies in a zGNR through the RKKY exchange interaction.