The objective of a base isolation system is to decouple the building from the damaging components of the earthquake by placing isolators between the superstructure and the foundation. In this paper, an optimum arrangement of lead rubber bearing (LRB) and friction pendulum system (FPS) is investigated in irregular buildings, and its performance is compared with a regular case. For this purpose, 3 types of irregularities according to ASCE/SEI 7–16 and 3 types of story buildings have been performed. Accordingly, various possible combinations have been applied for the isolators in each model. Afterward, the numerical models have been analyzed using nonlinear time-history analysis. The obtained results show that the application of FPS and LRB isolators in outer and inner columns led to better performance compared to the other arrangements. In this configuration, the inter-story drifts and base shear are reduced, and also the energy dissipation is increased more than in other arrangements. The reason for the superiority of the selected combination is due to the characteristics of FPS isolators in balancing the applied forces with the building’s mass and preventing torsion occurrence in irregular structures. Unlike the irregular buildings, the application of FPS and LRB isolators in inner and outer columns, result in better performance by reducing the story drifts in regular structures.