Balboa sailed to Hispaniola in 1501 on an expedition under Rodrigo de Bastidas and Juan de la Cosa. During this voyage they crossed the Gulf of Urabá (on the coast of present-day Colombia), and saw the Native American village of Darién in present-day Panama. In Hispaniola, Balboa settled down as a planter. However, he soon amassed a large amount of debt, and to escape from his creditors stowed away on a supply ship headed for San Sebastian on the Gulf of Uraiba, hidden in a cask. The ship was commanded by Martín Fernández de Enciso.
While under way, they met Francisco Pizarro (the later conqueror of Peru), who lead the colony in San Sebastian and told them almost all members of the colony had been massacred by the local people. Enciso nevertheless decided to go on to San Sebastian, but his ship was wrecked, the men being rescued by Pizarro but all supplies and livestock being lost. The colony was found in ashes. Balboa, by now accepted as a crew member of Enciso's, convinced them to try again in the area around Darién.
They subdued the local population, started a colony and built a village. Balboa made the colonists reject both Enciso's authority and that of Diego de Nicuesa, who was sent to Darién as governor after Enciso had sought redress with King Ferdinand. Balboa became de facto leader of the colony. Both the colony and Balboa himself thrived under his policies, making friends with surrounding peoples, and subduing and looting those who did not want to. He heard of a great sea on the other side of the mountains, and a land of great wealth (Birú, the Inca empire) to the south of this sea. As he heard that the king wanted to send him back to be tried for his conduct towards Enciso and Nicuesa, he decided he had to move fast.
On September 1, 1513, he sailed to San Blas (a lucky choice, as it just happens to be the smallest point of the isthmus), and went south across the isthmus. As before he befriended the locals who were so inclined, and captured, tortured and looted those that remained hostile, thus gaining substantial treasure. Finally he reached a top from where he could see the Pacific Ocean. When the others had joined him a Te Deum was chanted, a cross erected, and the sea was christened Mar del Sur (South Sea). He pushed on to the edge of the ocean, and Balboa claimed the ocean and all adjacent lands for Spain.
On the road back they captured a Native American chief called Tubanama and got a huge ransom, but some members almost died of hunger because they had loaded treasure in preference to provisions. On January 18, 1514, Balboa was back in Darién.
While Balboa was away, Pedro Arias de Ávila (generally known as Pedrarias) had been sent to Darién as a governor. Although this time Balboa did not oppose him openly, tension between them remained, Pedrarias being envious because Balboa was much more popular than himself. Balboa embarked on a new, courageous expedition by building ships on the Pacific coast. The transport of the materials across the isthmus cost the lives of many native slaves. Balboa made one expedition with the ships, to the Pearl Islands in the Gulf of Panama. He tried to head south from there, but found the wind unfavorable.
Pedrarias, being convinced that Balboa wanted to establish a government of his own on the west coast, had him arrested and tried for treason. Under pressure of Pedrarias Balboa was convicted and sentenced to death, and on January 21, 1519 Balboa was beheaded.