Indigenous people across South America tend to be multilingual, and South American languages exhibit historical contact effects that suggest multilingualism has long been an important part of the continent's social fabric. However, multilingualism, as it has unfolded in the Andes and Amazonia, has mostly not been considered within a single framework. This article discusses two patterns in the multilingualism identified by scholars of each region—regarding the role of hierarchical political formations and the importance of European colonial languages. It examines these patterns as they apply to a contemporary case of Quechua–Matsigenka–Spanish multilingualism in a highland–lowland transitional zone in Southern Peru. This case may be better understood as an integrated multilingual network rather than in terms of distinct and bounded macro‐regions. From this perspective, Andean and Amazonian situations may be more similar and closely integrated than is usually acknowledged. Attention to Andean–Amazonian connections adds to our understanding of the richness and variability of multilingualism in South America. [Amazonia, Andes, linguistics, Peru]