Reduced Ni (x) Mg1-x O solid solutions are promising catalytic materials for the dry reforming of methane with carbon dioxide, a reaction of tremendous importance that converts two green-house gases into syn-gas. Conventional nickel-based catalysts have been found to encounter carbon deposition (i.e., coking), one of the major resources that cause the catalyst deactivation. Previous studies suggested that MgO-supported Ni nanoparticles produced from the reduction of Ni (x) Mg1-x O can inhibit the accumulation of carbon. The efficiency and durability of the catalyst strongly depends on the morphology. Here we employed density functional theory to investigate the structural changes of the Ni (x) Mg1-x O(100) solid solution under different conditions. Our results show that Ni ions preferentially anti-segregate to the subsurface layers of the MgO matrix during the NiO-MgO intermixing. Under reducing conditions, Ni ions facilitates the generation of oxygen vacancies, which prefer to couple together with Ni ions inside the MgO matrix to form a Ni ion-oxygen vacancy pair. In addition, the segregation of a Ni ion-oxygen vacancy pair can be controlled by changing the concentrations of Ni ions. This is driven by the strong interaction between oxygen vacancies and Ni ions. It is well known that oxygen vacancies play an important role during a catalytic reaction on an oxide, providing active sites to help the adsorption and dissociation of reaction intermediates. Our results show that in mixed oxides oxygen vacancies could also drive the segregation of the catalytically active components and provide new opportunities to tune the catalytic activity of oxides.