Recently, incorporating guanidium (GA) cations into organolead halide perovskites is shown to effectively improve the stability and performance of the solar cells. However, the underlying mechanisms that govern the GA incorporation have remained unclear. Here, FAPbI3 is used as a basic framework to investigate experimentally and theoretically the role of cesium (Cs) and bromine (Br) substitutions in GA+ incorporation. It is found that simultaneous introduction of the small-size Cs+ and Br– in the FAPbI3 lattice is critical to create sufficient space for the large GA+ and that the presence of the Cs+ prevents the formation of a GA-contained low-dimensional phase, which both assist GA+ incorporation. Upon entering the perovskite lattice, the GA+ can stabilize the lattice structure via forming strong hydrogen bonds with their neighboring halide ions. Such structure modification suppresses halide vacancy formation, thus leading to improved material properties. Compared to the GA-free perovskite reference samples, the optimal system GA0.05Cs0.15FA0.8Pb(I0.85Br0.15)3 exhibits substantially improved thermal and photothermal stability, as well as increased photocarrier lifetime. Solar cells fabricated with the optimal material system show an excellent photovoltaic performance, with the champion device reaching a power conversion efficiency of 21.3% and an open circuit voltage of 1.229 V.