Among the Old World hystricognathous rodents, the phylogenetic relationships between the Palaeogene (“Phiomyidae”, Baluchimyinae”, Gaudeamuridae) and Neogene/Recent families (Diamantomyidae, Kenyamyidae, Myophiomyidae, Thryonomyidae, Bathyergidae, Petromuridae, and Hystricidae) had never been properly assessed. Here we have investigated these relationships in performing a cladistic assessment of the dental evidence in order to better understand the macroevolutionary pattern of Old World hystricognaths during the Tertiary, and to determine to which fossil groups the modern “phiomorph” families (Thryonomyoidea) are potentially closely related. From our phylogenetic results, it appears that Old World hystricognaths have experienced significant turnovers during the Tertiary. “Phiomyidae”, “Baluchimyinae”, Diamantomyidae, Kenyamyidae and Myophiomyidae are outside the crown radiation and were parts of earlier and successive extinct radiations. Eocene-Oligocene “Baluchimyinae” and “Phiomyidae” are extinct stem lineages of an initial middle Eocene radiation of hystricognaths, while Oligocene-Miocene Diamantomyidae, Kenyamyidae and Myophiomyidae are extinct stem lineages of a second radiation of hystricognaths that occurred during the early Oligocene. Although the earliest known stem Thryonomyidae and Bathyergidae are exclusively early to middle Miocene in age, our phylogenetic pattern suggests that these crown hystricognaths (thryonomyoid “phiomorphs”) diversified at least by the latest Oligocene. The extant Hystricidae would be nested within the extinct Palaeogene Gaudeamuridae and both would share a common ancestry with the New World hystricognaths (caviomorphs). In this context, hystricids would appear as a long-lived lineage of modern Old-World hystricognaths. It is noteworthy that the main radiations observed here coincide with periods of global climatic changes (MECO, EOBc and LOW). In a notable implication, the MECO would have also driven the early biogeographic history of hystricognaths between South Asia and Africa, but also between Africa and South America.