The beginning of plant cultivation is one of the most important cultural transitions in human history1–4. Based on molecular markers showing the genetic similarities between domesticated plants and wild relatives, south-western Amazonia has been proposed as one of the early centres of plant domestication4–6. However, the nature of the early human occupation and the history of plant cultivation in south-western Amazonia are still little understood. Here, we document the cultivation of Cucurbita at ca. 10,250 cal yr BP, Manihot at ca. 10,350 cal yr BP and Zea mays at ca. 6,850 cal yr BP in the Llanos de Moxos. We show that, starting ca. 10,850 cal yr BP, pre-Columbians created an anthropic landscape made of approximately 4,700 artificial forest islands within a treeless seasonally flooded savannah. Our results confirm the Llanos de Moxos as a hotspot for early plant cultivation and demonstrate that ever since their arrival, humans have caused a profound alteration of Amazonian landscapes, with lasting repercussions for habitat heterogeneity and species conservation.