In wild rodent populations, arenaviruses and the retrovirus MMTV both utilize the host Transferrin Receptor 1 (TfR1) for cellular entry. We show that the physical interactions between the surface glycoproteins of these viruses and TfR1 has been highly dynamic over time, leading to an evolutionary arms race that has shaped the protein sequences of both TfR1 and virus glycoproteins for millions of years. Evolutionary analysis of only eight rodent TFR1 gene sequences allowed us to quickly identify specific residues in TfR1 that mediate patterns of viral host range. We also gained additional insight into the host ranges and origins of these viruses. Based on our analyses, we predicted that MMTV-like retroviruses, which are restricted to rodents of the genus Mus, once circulated widely among rodent genera. We verified this through identification of endogenous MMTV-like genomes “fossilized” in the genome of a former host. This evolutionary approach can theoretically be applied to the study of any host-virus interaction. As such, this is a scalable framework for understanding the host range of viruses emerging from wildlife reservoirs.