The valley was originally populated by people of the Chane culture dedicated to agriculture, hunting and gathering. The Chanes are famous for their densely populated villages, their ceramics and graphic designs, and most importantly the construction of the temple at El Fuerte de Samaipata. They cultivated mainly corn and peanuts, and were rather peaceful. There are several Chane burial sites all through the valleys and pampas of Santa Cruz between the Siberia mountain ridge and the Guapay river.
The region was later conquered by Incas as they expanded to the southeast from their native Peru. The Incas reached a pact with the Chanes and built a city at El Fuerte de Samaipata.
The Guarani warrior tribes coming from the south invaded the valley and defeated both Incas and Chanes. The Guarani hordes kept raiding the valley and the nearby region well into the Spanish colonial times.
In 1618, Pedro de Escalante y Mendoza founded Samaipata, as point of contact between Santa Cruz and Vallegrande. The town moved from its original location in a place known as Castilla to its current location a few kilometers west