In the meantime Pizarro quitted St Sebastian with a small remnant of the unfortunate colony, and escaped with much difficulty to Carthagena, where, by good fortune for him, Enciso had just arrived with two ships and a considerable reinforcement. He took Pizarro on board, and they returned to St Sebastian, where they had the misfortune to run their ships aground, and after getting on shore with much difficulty, they found the place reduced to ashes by the savages. They restored it as well as they could, and got on shore all the provisions and stores from their stranded vessels, but were soon afterwards reduced to the utmost extremity of distress by war and famine. Hunger frequently forced them out into the country to endeavour to procure provisions, and the savages as often drove them back with the loss of some of their number, which they could very ill spare, having only been 180 men at the first They were relieved from their present distressed situation, by the dexterity and presence of mind of a very extraordinary person who happened to be among them. Vasquez Nugnez de Balboa, the person now alluded to, was a gentleman of good family, great parts, liberal education, of a fine person, and in the flower of his age, being then about thirty-five. He had formerly sailed on discovery along with Bastidas, and had afterwards obtained a good settlement in Hispaniola; but had committed some excesses in that island, for which he was in danger of being put to death. In this extremity, he procured himself to be conveyed into the ship commanded by Enciso, concealed in a bread cask, in which he remained for some days, and at last ventured to make his appearance, when the ship was 100 leagues from Hispaniola. Enciso had been strictly enjoined not to carry any offenders from the island, and now threatened to set Balboa ashore on the first desert island; but the principal people on board interceded for him with the captain, who at last relented and granted him protection. This did not efface from his memory the threats of Enciso, as will be seen hereafter. Observing the state of despair to which the company was now reduced, Balboa undertook to encourage them, by asserting that their situation was not so helpless as they imagined. He told them that he had been upon this coast formerly with Bastidas, when they sailed to the bottom of the gulf, where they found a fine large town, in a fruitful soil and salubrious climate, inhabited indeed by warlike Indians, but who did not use poisoned arrows. He exhorted them, therefore, to bestir themselves in getting off their stranded vessels, and to sail to that place. They approved of this advice, and sailed to the river named Darien by the Indians, where they found every thing to correspond with the description given by Balboa. On learning the arrival of the Spaniards, the natives secured their wives and children, and waited on a little hill under their cacique, named Cemano, for the attack of the Spaniards. After having performed their devotions, the Spaniards fell resolutely on the Indians, whom they soon routed; and then went to the town, which they found full of provisions to their wish. Next day, they marched up the country among the neighbouring mountains, where they found many empty houses, all the inhabitants having fled; but they found the houses well replenished with household goods of various kinds, such as earthen vessels, cotton garments like short petticoats for women, a great deal of cotton, both spun and unspun, plates of gold which the natives wear on their breasts, and many other things, amounting in all to the value of 10,000 pieces of fine gold. Enciso was greatly rejoiced at this unexpected good fortune, and immediately sent for the rest of the men, who had been left on the other side of the bay, because the brigantines could not carry the whole at once. Balboa gained much reputation by the success of this enterprize, and was henceforwards held in high esteem by the people.

The whole party agreed to establish a colony at this place, which they named Santa Maria el Antiqua del Darien, the first part of the name being that of a church in Seville, and Darien being the Indian name of the river. Balboa being now in great credit with the colonists, and brooding revenge for the former threats of Enciso, secretly plotted to deprive him of the command, alleging that they were now beyond the limits of Hojedas government, who had no authority in this place. While this was in agitation, Enciso thought proper to prohibit all the colonists from trading with the Indians for gold, under pain of death; but they, believing that he did this entirely for his own advantage, unanimously threw off all subjection to his authority, alleging that his command was void for the reasons already mentioned, and others. They then proceeded to choose alcaldes and regidores, being the titles of the chief magistrates in the towns of Old Spain, and Balboa and Zamadio were elected alcaldes, and Yaldibia regidore. The people, however, were dissatisfied with this mode of governing, repenting that they had deposed Enciso, and the whole colony divided into parties. One party alleged that it was not proper to be without a commander in chief, and that Enciso ought to be restored till another governor was appointed by the king: A second party said that they ought to submit to Nicuessa, because the place they were in was within his grant. The third party, being the friends of Balboa, wished to continue the present frame of government; but if the majority were for a single commander, they insisted that Balboa ought to have the command.

In the midst of these disputes, Roderic Enriquez de Colmenares arrived with two ships, having on board provisions, military stores, and seventy men. This captain had met with a great storm at sea, and had put into the port of Santa Maria, which the Indians call Gayra, 50 or 60 leagues from Carthagena. On the boats going on shore for water, the cacique came forwards with twenty of his people, dressed in a kind of cotton cloaks, though the natives of that part of the coast usually go naked. He advised them not to take water from the place where they were, saying that it was not good, and offered to shew them another river of better water. But on coming to it, they could not get their boats to the place, owing to a heavy surf, and returned to the first place. While filling their casks, about seventy armed Indians rushed suddenly upon them, and before the Spaniards could stand to their defence, forty-five of them were wounded by poisoned arrows. The wounded men swam off to the ships, as the Indians had staved their long-boat, and all of them died save one. Seven of the Spaniards saved themselves in a large hollow tree, intending to swim off at night; but those on board supposing them all killed, sailed away much dejected, for Uraba, to inquire after Nicuessa. Finding no person on the east side of the bay, where they thought to have found either their own men or those belonging to Hojeda, Colmenares suspected they were all dead, or had gone to some other place; but he thought fit to fire off some cannon, that they might hear him if still in the neighbourhood; besides which he made fires at night, and smokes by day on some of the adjacent high rocks. The people at Santa Maria el Antiqua del Darien heard his guns, which resounded through the whole bay to the westwards, and making signals in return, he came to them about the middle of November 1510. Colmenares distributed his provisions among the colonists of Darien, by which he gained the good will of most of those who had opposed the calling of Nicuessa to the command, whom they now agreed to send for that he might assume the government.