The central nervous system (CNS) carries a variety of immune cells including macrophages, which can be divided based on their localization: microglia are found in the parenchyma, whereas the CNS interfaces such as meninges and perivascular spaces host CNS border-associated macrophages (CAMs). To date, in contrast to that of microglia, the nature of CAMs is poorly understood. In the present study, we investigated the distribution of CAMs during development and revealed previously-unappreciated kinetics of CAM subpopulation. Furthermore, we identified Irf8 and Mafb as crucial transcription factors for the establishment of CAMs, as well as microglia. Together, our data reveal a novel process and molecular machinery for the establishment of CNS macrophage subsets during development.