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The city was first founded in 1561 by Spanish explorer Ñuflo de Chavez about 200 km (124 mi) east of its current location, and was moved several times until it was finally established on the Pirai River in the late 16th century.For much of its history, Santa Cruz was mostly a small outpost town, and even after Bolivia gained its independence in 1825 there was little attention from the authorities or the population in general to settle the region.Shortly after the founding, attacks from local tribes became commonplace and Ñuflo de Chaves was killed in 1568 by Itatine natives.After Chaves's death, the conflicts with the local population as well as power struggles in the settlement forced the authorities in Peru to order the new governor, Lorenzo Suarez de Figueroa to relocate the city to the west.Animosity towards imperial authorities began at the turn of the 18th century when the new system of intendencias reached the new world.
The settlement was named after Chaves's home town in Extremadura, where he grew up before venturing to America.
It was not until after the middle of the 20th century with profound agrarian and land reforms that the city began to grow at a very fast pace.
The city is Bolivia's most populous, produces nearly 35% of Bolivia's gross domestic product, and receives over 40% of all foreign direct investment in the country.
After they moved the city was finally consolidated in 1622 and took its original name of Santa Cruz de la Sierra given by Ñuflo de Chaves over 60 years before.
Remnants of the original settlement can be visited in Santa Cruz la Vieja ("Old Santa Cruz"), an archaeological site south of San José de Chiquitos.