European colonization of South America instigated a continental-scale depopulation of its indigenous peoples. The impact of depopulation on the tropical forests of South America varied across the continent. Furthermore, the role that indigenous peoples played in transforming the biodiverse tropical forests of the Andean–Amazonian corridor before AD 1492 remains unknown. Here, we reconstruct the past 1,000 years of changing human impact on the cloud forest of Ecuador at a key trade route, which connected the Inkan Empire to the peoples of Amazonia. We compare this historical landscape with the pre-human arrival (around 44,000–42,000 years ago) and modern environments. We demonstrate that intensive land-use within the cloud forest before European arrival deforested the landscape to a greater extent than modern (post-AD 1950) cattle farming. Intensive indigenous land-use ended abruptly around AD 1588 following a catastrophic population decline. Forest succession then took around 130 years to establish a structurally intact forest—one comparable to that which occurred before the arrival of the first humans to the continent. We show that nineteenth-century descriptions of the Andean–Amazonian corridor as a pristine wilderness record a shifted ecological baseline—one that less than 250 years earlier had consisted of a heavily managed and cultivated landscape.