The very recent success of Xie et al. (Nat. Commun., 2017, 8, 14827) in achieving the Ir-catalyzed direct borylation of the cage B(3,6)–H of o-carboranes with excellent yield and regioselectivity represents an exciting development in the regioselective functionalization of carboranes. In the present work, the possible catalytic mechanisms and ultimate origin of regioselectivity were studied in detail by using the DFT method. The computational results show that the Ir^III species should be the actual catalyst, rather than the Ir^I compound as supposed from the experiments. Every borylation cycle occurs via two successive oxidative addition–reductive elimination (OxA–ReE) processes, including an unusual Ir^V species in each process. The regioselectivity is determined in the first OxA step of each borylation. Two reaction conformations were calculated and concluded to be competitive. Different distributions of the C–H⋯O hydrogen bonds and B–H⋯O “interactions” were disclosed to be mainly responsible for the different energy profiles of the two reaction conformations. Localized orbital locator (LOL) analysis showed a 26-electron-delocalization structure of the o-carborane, which is considered the fundamental reason for the aromaticity and exceptional chemical stability of this series of carborane (anions). The highly electron-delocalized structure together with the inductive effects of the carbon centers makes the B(3,6)–H sites most electron deficient, resulting in these being the most favorable sites for the OxA reaction to occur with the Ir^III species. This was concluded to be the ultimate origin of the regioselectivity of the title reaction. We believe the present work should be very attractive for experimental scientists since it could be of great help guiding them in the rational design of more efficient catalytic borylation reactions of carboranes with better regioselectivities.