Arthropod-borne viruses, such as dengue, Zika, and Mayaro, are emerging at an accelerating rate in the neotropics. The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO) project, a part of the NIH-funded Centers for Research in Emerging Infectious Diseases (CREID) network provides a nimble and flexible network of surveillance sites in Central and South America coupled with cutting-edge modeling approaches to anticipate and counter these threats to public health. Collected data and generated models will be utilized to inform and alert local, regional, and global public health agencies of enzootic arboviruses with a high risk of spillover, emergence, and transmission among humans, and/or international spread. CREATE-NEO builds capacity in situ to anticipate, detect, and respond to emerging arboviruses at the point of origin, thereby maximizing the potential to avert full-blown emergence and widespread epidemics.