This article examines the shifting nature of interethnic relations between two indigenous groups in Amazonian Ecuador, the Curaray River group of lowland Kichwa and the neighboring Waorani of the Curaray region. Waorani and Curaray Kichwa interaction from the 1930s to the present reveals a pattern marked by oscillations between hostilities and cautious friendship. These shifts are expressed in varied social relations described in the anthropological and historical scholarship on Amazonia, ranging from shamanic attack to marriage alliances. The paper explores this history and its linkage to wider social changes in the region brought about by Protestant evangelization and international economic interests. Our ethnographic analysis points to the maintenance of extended family linkages between Kichwa and Waorani in the Curaray River region as nodal relationships that potentiate shifts from hostilities to friendship between the two indigenous groups. These shifts occur within a regional interaction sphere that is bound together by extended family ties between specific household groups. By examining these relations through the lenses of both Waorani and Curaray Kichwa ethnography and of historical processes extending back almost a century, the article provides insights into a complex sociality involving distinct indigenous peoples across a multiethnic region of the Western Amazon.