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Seoul orthohantavirus (SEOV) has been identified as one of the main causative agents of hemorrhagic fever with renal syndrome (HFRS) in China. The virus was found circulating in rodent populations in almost all provinces of the country, reflecting the wide distribution of HFRS. Here, using the direct immunofluorescence assay (DFA) and real-time quantitative reverse transcription PCR (qRT-PCR) approach, we performed screening in 1784 small mammals belonging to 14 species of three orders captured in the main areas of HFRS endemicity in Yunnan province (southwestern China) and identified 37 SEOV-positive rats (36 Rattus norvegicus and 1 Rattus tanezumi). A 3-year surveillance of HFRS epidemics and dynamics of rodent reservoir density and virus prevalence implied a potential correlation between them. The subsequent meta-transcriptomic sequencing and phylogenetic analyses revealed three SEOV variants, among which two are completely novel. The ancestral character state reconstruction (ACSR) analysis based on both novel variants and documented strains from 5 continents demonstrated that SEOV appeared to originate near the southwestern area (Yunnan-Kweichow Plateau) of China, then could spread to other regions and countries by their rodent carriers, resulting in a global distribution today. In summary, these data furthered the understanding regards genetic diversity and the potential origin for SEOV. However, the expanding endemic foci in the province suggest that the virus is spreading over a wider region and is much more diverse than previous depicted, which means that increased sampling is necessary. Author summary: Hantaviruses are primarily hosted by small mammals such as rodents, shrews, moles, and bats. In recent years, the diseases caused by rodent-associated hantaviruses become more frequent among humans in Yunnan province. In order to curb human infections, it is necessary to monitor the dynamics of virus prevalence in their natural reservoir populations. As expected, we detected 37 SEOV strains harbored by rats in the main endemic areas of the province, and the subsequent meta-transcriptomic and phylogenetic analyses revealed two SEOV variants that diverged early from the rest of the viruses, based on which Yunnan-Kweichow Plateau appears to be the region where earlier SEOV was originated. Further studies and more samples are needed to clarify how the virus migrates worldwide, and the pathogenicity of newly discovered viruses. [ABSTRACT FROM AUTHOR]