Chagas disease, caused by the vector-borne parasite Trypanosoma cruzi, remains one of the most significant neglected tropical diseases affecting the Americas. Identifying high-risk populations is important for understanding Chagas disease transmission and directing public health resources. We recently hypothesized that Texas hunters may be at an elevated risk for contracting Chagas disease because of opportunities for vector exposure and contact with blood of infected reservoirs. To assess their unique exposure risks, we conducted a statewide screening program of Texas hunters. A total of 885 study participants were interviewed and tested for T. cruzi infection; 18 screened positive on a rapid, point-of-care test; however, none were found positive through confirmatory testing. We did find a high prevalence of reported direct contact with wildlife blood as well as triatomine and other arthropod disease vectors. This large-scale screening program represents a novel approach to better understand the vector-borne disease risk in this unique population.