Its closest living relatives are of the genus Apodemus, which includes the field and wood mice.

The ancestors of Rhagamys, belonging the widespread genus Rhagapodemus, first arrived in Corsica-Sardinia during the Early-Late Pliocene transition, around 3.6 million years ago.

[5] Before the arrival of humans on the islands in about 8000 BC, Corsica and Sardinia had their own highly endemic depauperate terrestrial mammal fauna which besides Rhagamys orthodon included a species of dwarf mammoth (Mammuthus lamarmorai), the Tyrrhenian vole (Microtus henseli), the Sardinian pika (Prolagus sardus), the shrew Asoriculus similis, a mole (Talpa tyrrhenica), the Sardinian dhole (Cynotherium sardous), a galictine mustelid (Enhydrictis galictoides), three species of otter (Algarolutra majori, Sardolutra ichnusae, Megalenhydris barbaricina) and a deer (Praemegaceros cazioti).

[6] The small mammals, including Rhagamys, persisted for many thousands of years after the first human arrival on the islands, with the youngest radiocarbon date for Rhagamys on Sardinia being around 822-776 BC, while on Corsica the youngest dates for the species are around 393 BC.

The cause of the extinction is unknown, but may be due to invasive species introduced by new arrivals to the islands such as Carthaginians and the Romans.