High species diversity is often associated with historical and ecological factors. However, how these factors interacted synergistically to shape the patterns of species diversity remains poorly understood. Here, we investigate the diversification patterns of the Gyrostemonaceae-Resedaceae-Forchhammeria-Tirania (GRFT) clade (Brassicales) and the potential driving mechanisms by integrating historical and ecological factors. Our results indicate that the most recent common ancestor of the GRFT clade occupied humid habitats in Australia and Southeast Asia in the early Eocene and then dispersed into the Mediterranean region and Central America in the middle to late Eocene. The northward movement of the Indian subcontinent, sea-level fluctuations, the formation of the North Atlantic Land Bridge, and associated climate changes might have driven the early biogeographic diversification of the GRFT clade. Within Resedaceae, we inferred seven dispersal events of out of the Mediterranean region, suggesting that the Mediterranean region was an important source for the diversity of Resedaceae and likely for other arid-adapted lineages in the Old World. The xeric Resedaceae underwent an increase in diversification rates in the Old World after the late Oligocene. This temporally coincided with the appearance and expansion of arid habitats in western Eurasia and Africa, which resulted from regional orogenetic and climatic changes. Furthermore, climatic niche divergence has contributed to higher species diversity of Resedaceae compared to other lineages in the GRFT clade. Our study provides a case exploring evolutionary and climatic mechanisms underlying species diversity patterns of a group, and suggests that past geoclimatic changes and niche differentiation possibly drove jointly the diversification of the GRFT clade.