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| 1537 |
| | With the end of the siege of Cuzco, and the flight of Manco Inca, the Spanish have full control of Peru | |
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| 1542 |
| | New Laws are passed in Spain, in an attempt to protect the Indians on the encomiendas of Spanish America | |
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| 1545 |
| | Rich seams of silver are discovered at Potosi, in modern Bolivia | |
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| 1548 |
| | La Paz is founded on the trade route between Lima and the newly discovered silver mines at Potosi | |
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| c. 1550 |
| | Spanish galleons assemble each year at Portobelo to deliver European goods and to ship home the metals of Latin America | |
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| 1556 |
| | Charles V abdicates, handing the Netherlands and Spain to his son Philip and the title of Holy Roman emperor to his brother Ferdinand | |
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| 1556 |
| | The division by Charles V of his territories means that there are now two Habsburg empires, Austrian and Spanish | |
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| 1571 |
| | The Spanish governor general, Legazpi, makes his capital at Manila,and names the surrounding islands the Philippines after Philip II | |
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| 1571 |
| | The Philippines and its governor general are placed under the authority of the Spanish governor of New Spain, ruling from Mexico City | |
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| 1571 |
| | Spanish and Venetian galleys defeat the Turks in the battle of Lepanto | |
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