Pizarro set sail in Alonzo de Ojeda's expedition to the Gulf of Uraba in the New World in 1509. After its failure he joined the fleet of Martin Fernandez de Enciso in 1513.
In 1514, Pedrarias Davila succeeded Vasco Nunez de Balboa as the governor of Castilla de Oro. Pizarro became a close associate of the governor over the next five years and arrested Balboa on the governor's order. For his loyalty, Pizarro was made the mayor and magistrate of the recently founded Panama City for four years.
In 1524, he teamed up with navigator Diego de Almagro and a priest Hernando de Luque to explore the western South America with 80 men and 40 horses. The first expedition turned out to be a failure as they encountered bad weather, scarcity of food and hostile natives.
In 1526, they went on a second expedition, with two ships carrying 160 men and several horses. On reaching the San Juan river, Almagro headed back to Panama for reinforcements and Bartolome Ruiz, the main pilot kept heading south.
Ruiz captured a raft laden with textiles, ceramic objects and gold and silver pieces. He went back north to Pizarro and told him about the discovery. Rejuvenated with the news and thrilled by the reinforcements, Pizarro went south but did not advance to the mainland as the natives looked dangerous and threatening.
Almagro returned to Panama to gather more reinforcements but the new governor, Pedro de los Rios called off the expedition after the second unsuccessful trial. He sent two ships commanded by Juan Tafur to bring back all the men at once.
All but Pizarro and 13 others (The Famous Thirteen) came back to Panama. These men remained at the La Isla Gorgona for seven months. The governor sent one more ship to bring Pizarro back, but Almagro and Luque boarded the ship to join Pizarro and further their expedition.
They reached Tumbes in 1528 and saw the incredible riches the place was bestowed with. They planned to go back to Panama and prepare for the final expedition of conquest. Two native boys, Felipillo and Martinillo, came along to learn their language.
The governor refused the third expedition to Panama. So Pizarro went to Spain and appealed to King Charles I himself. The king expressed his support but had to leave for Italy. In his absence, Queen Isabel signed the Capitulacion de Toledo in July 1529.
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One condition in the grant was that Pizarro would establish a force of 250-sufficiently equipped men in six months. Pizarro went to Trujillo to ask his half-brothers and other men to accompany him in his expedition.
The final expedition left in December 1530 with three ships, 180 men and 27 horses. He was also accompanied by Francisco de Orellana and Hernando, Juan and Gonzalo Pizarro.
On the way to Tumbes, Pizarro was forced to confront the Punian natives and suffered losses. Soon Hernando se Sato joined the expedition with a 100 volunteers and horses. After reaching Tumbes, they saw it was ransacked.
In search of a safe place, they headed into the interior land in 1532 and established San Miguel de Piura, the first Spanish settlement in Peru. Pizarro headed along with 200 men to Zaran. De Sato was dispatched to a Peruvian garrison at Caxas and he came back a week later with an envoy from the Inca, Atahualpa.
Atahualpa was asked to pay tribute to the Emperor Charles but he refused. Then Pizarro and his forces attacked the 6000 strong Inca army. Atahualpa was taken captive, and despite having paid a ransom to spare his life, he was executed in 1533. This move angered a lot of people including the king, Pizarro and de Sato.
In 1534, Jauja in the Mantaro Valley was established as Peru's provisional capital. However it was too far from the sea to serve as the Spanish capital of Peru. Thus Pizarro founded the city of Lima as the new capital of Peru in 1535.
During the late 1530s, relations between Pizarro and Almagro became strained over disputes regarding their claims in the new Spanish province. While the king of Spain had awarded the Governorate of New Toledo to Almagro and the Governorate of New Castile to Pizarro, both the men wanted to claim the city of Cuzco.
These disputes between the former allies culminated in the Battle of Las Salinas in 1538. Pizarro’s forces won the battle and captured Almagro who was later executed.