American trypanosomiasis is a public health problem in Latin America and southern parts of the United States. Infection in triatomines (vector) and domestic dogs (reservoir host) is a good indicator of Trypanosoma cruzi circulation and human risk of infection. The State of Mexico, Mexico, has been considered free of T. cruzi, and no detailed epidemiologic study has been conducted to assess the intricacies of the transmission cycle of the parasite in the region. Such studies would enhance our understanding of the epidemiology of T. cruzi infection in this geographic region and provide regional sanitary authorities with stronger fundamental knowledge for making decisions and allocating funds for Chagas disease control programs in the State of Mexico. The objective of this study was to determine the prevalence of T. cruzi infection in dogs (seroprevalence) and triatomines (fecal parasites) in a previously identified, discrete endemic region of parasite circulation and to widen our studies in the Tejupilco Sanitary Region located in the southern part of the State of Mexico. Dog blood samples (n=102) were analyzed for the presence of anti-T. cruzi antibodies by two assays, namely indirect hemagglutination assay and enzyme-linked immunosorbent assay. Triatomines (n=88) were collected and fecal aliquots were analyzed for the presence of parasites by light microscopy. Average seroprevalence in dogs in the Tejupilco Sanitary region was 24.5%, and the overall triatomine infection rate was 34.01%. Triatoma pallidipennis was the only triatomine species found in this region. Our data demonstrate that T. cruzi is actively circulating in the Tejupilco Sanitary Region and emphasize the requirement for epidemiologic surveillance programs throughout the putative endemic areas of the State of Mexico.