Omsk hemorrhagic fever (OHF) is a severe disease that emerged in the 1940s in Siberia, Russia. It is caused by the OHF virus (OHFV), belonging to the Flavivirus genus. In wildlife, the principal vector of OHFV is the Dermacentor reticulatus tick. However, humans are mainly infected after contact with an infected muskrat Ondatra zibethicus. The evolutionary history of OHFV is not yet clarified. In an attempt to reconstruct the temporal and spatial phylodynamics of OHFV, a collection of 25 OHFV strains was studied. Maximum likelihood analysis, the Bayesian MCMC approach, and procedures based on continuous-time Markov Chain process, were used for the investigation of OHFV E gene nucleotide sequences. Six statistically supported clusters of OHFV were identified; five of them joined in a main clade A. The first revealed evolutionary event, when OHFV clade A and clade B divided, dated to about 700 years ago. Clusters C, D, and E, within clade A, separated 230 years ago and further evolved during last century. The phylogeographic analysis showed that clade A originated in the Omsk Province, whereas clusters B, C, and E appeared to originate in Kurgan, Novosibirsk, and Omsk Provinces, respectively. In conclusion, OHFV, as a member of the mammalian tick-borne group of flaviviruses, evolved in Western Siberia during the last millennium. When a highly susceptible species, O.zibethicus, was introduced into the region, in the 1930s, OHFV used this species as an amplifying host that lead to numerous fatal epizootics in muskrats and to human OHF outbreaks.