Abstract: Top-down processes of regional integration among the Andean countries of South America are occurring alongside bottom-up processes of Indigenous regionalism in Bolivia and Ecuador that weave together Indigenous peoples’ territories across local administrative units and even national borders. In light of this dynamic, the study asks: What explains the new Indigenous regionalism in the Andes? And, what are its implications for formal processes of regional integration? The study examines the cases of the Coordinator of Indigenous Organizations of the Amazon River Basin (COICA) and the National Council of Ayllus and Markas of Qullasuyo (CONAMAQ) as examples of Indigenous regionalism in relation to the institutional innovations of the Andean Community of Nations (CAN) to incorporate Indigenous organizations into its structure and agenda. The article argues that the intersections of regional integration, the enactment of the plurinational state, and Indigenous autonomies have provided the necessary institutional space for expressions of Indigenous regionalism to flourish.