Crimean-Congo hemorrhagic fever (CCHF) is a prevalent tick-borne disease in different regions of Iran. This molecular and serologic study was performed to investigate the Crimean-Congo hemorrhagic fever virus (CCHFV) in collected ticks and in blood samples of some domestic animals in North Khorasan, Northeast of Iran. In this cross sectional study, 136 blood samples from domestic animals (sheep, goats, and cows) collected in the Northeast region in Iran were examined using IgG ELISA assay. Ticks (n = 1478) were collected from sheep, goats, and cows. Out of all collected ticks, 62 specimens were investigated for CCHF virus genome using RT-PCR technique. The data were descriptively presented by median and 95% confidence interval (CI). CCHFV infection rate was 8.1% in studied ticks. Two species of ticks, Hy. anatolicum (n=3; 15%, 95% CI 9.41-20.59) and Rh. sanguineus (n=2; 6.9%, 95%CI 4.33-8.58), were infected with CCHFV genome and were probable vectors of CCHF virus in the area. Infection rate was 15.4% for CCHFV in tested domestic animals. Serologic tests detected CCHFV specific IgG antibodies in 16.2% (95% CI 13.49-18.83) (99/16) and 19.2% (95% CI 13.26-25.20) (26/5) of sheep and goats, respectively. The present study showed that domestic animals and ticks were infected with Crimean-Congo hemorrhagic fever virus and that the disease was endemic in North Khorasan province, Iran. However, further surveillance and prevention programs are recommended.