Severe fever with thrombocytopenia syndrome (SFTS), an emerging high-fatality infectious disease, is caused by a novel bunyavirus. However, a clear natural transmission model has not yet been established. We conducted a cross-sectional study with in-depth investigation of villages to systematically understand the transmission and risk factors among humans, host animals, and vectors. Village residents were interviewed using standardized questionnaires, in which there were confirmed cases of new infections, between August 2012 and May 2013. Serum samples from all villagers and animals, as well as tick specimens, were collected for qRT-PCR and antibody testing. The seropositivity rate among villagers was 8.4% (35/419), which was lower than that among domesticated animals (54.0%, 27/50; χ(2)= 81.1, P < 0.05). SFTS viral RNA was most commonly detected among domesticated animals (14.0%), followed by ticks (3.1%) and humans (1.7%; χ(2) = 23.1, P < 0.05). The homology of the S gene fragment was 98%. Tick bites were significantly associated with SFTSV infection (Conditional Logistic Regression odds ratio [OR] = 2.5, 95% confidence interval [CI], 1.0-6.6). We provided systematic evidence on a natural transmission model for SFTSV from reservoir hosts (domesticated animals) to vectors (Haemaphysalis longicornis) to humans, and close contact with SFTS confirmed patients was not found to be a risk factor for natural transmission.