Although ~30 hypotheses or theories have been proposed to explain global species richness and its large-scale spatial arrangement in the marine and terrestria lrealms, a scientific consensus has not been reached yet. Here we use a multidisciplinary approach coupling a paleoclimatic and a macroecological model to show that the niche-environment interaction is fundamental to explain how global species richness has varied during the Phanerozoic Eon and how the resulting large-scale biodiversity patterns have been shaped through time. Although our model identifies a major mechanism, it also suggests that the nicheenvironment interaction is itself modulated by global climate, a mid-domain effect in the niche space, the position of the land masses, the global area available around continents and habitat fragmentation that affect environmental heterogeneity, which in turn promotes allopatric speciation that controls the global pool of species. Our study therefore demonstrates that any unifying theory on global biodiversity should consider a large number of factors that controls not only biogeographic biodiversity patterns but also their changes through deep time.