Musical instruments provide material evidence to study the diversity and technical innovation of music in space and time. We employed a cultural evolutionary perspective to analyse organological data and their relation to language groups and population history in South America, a unique and complex geographic area for human evolution. The ethnological and archaeological native musical instrument record, documented in three newly assembled continental databases, reveals exceptionally high diversity of wind instruments. We explored similarities in the collection of instruments for each population, considering geographic patterns and focusing on groupings associated with language families. A network analysis of panpipe organological features illustrates four regional/cultural clusters: two in the Tropical Forest and two in the Andes. Twenty-five percent of the instruments in the standard organological classification are present in the archaeological, but not in the ethnographic record, suggesting extinction events. Most recent extinctions can be traced back to European contact, causing a reduction in indigenous cultural diversity.