Before the arrival of the conquistadores in the 16th Century the area was populated by ethnic Sanavirónes and Mocovíes.
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It lay on an alternative route to the mining region of Potosí in Peru, it was used as a market for contraband such as slaves to work in the mines and silver.
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In 1891 the first railway arrived in Morteros, the railway brought a large number of European immigrants from the Piamonte, Friuli and Toscana in Italy.