Over the last three decades, the first continuous road has been paved to connect northern South America’s Atlantic and Pacific coasts. The final sections of this Inter-Oceanic Highway are now being completed through the western Amazon Basin, a global biodiversity hotspot, at the triple-border of Brazil, Bolivia and Peru. Satellite images from 1989, 2000, and 2007 reveal accelerating clearing across the region, but the countries’ prior infrastructures governed their individual responses to the road. Brazilian deforestation slowed as the frontier expanded away from the highway with a network of capillary roads, but Bolivian clearing accelerated as its urban centers sprawled toward the road. Peru’s forests remain relatively intact, but similar trends isolated from Brazil suggest imminent acceleration as Peruvian infrastructural capacity increases.