When De Castro was informed of the critical situation of affairs in Chili, he immediately sent off a considerable reinforcement by land under the command of Monroy, who had the good fortune to conceal his march from the Copaipans, and to join Valdivia in safety. At the same time the president of Peru dispatched by sea Juan Batista Pastene, a noble Genoese, with a more considerable reinforcement for Valdivia. On receiving these two reinforcements, which arrived about the same time, Valdivia began to carry his great designs into execution. Being solicitous to have a complete knowledge of the sea-coast, he ordered Pastene to explore the whole as far to the southwards as possible, noting the most important places all along the coast; and, on his return from this maritime survey, he sent him back to Peru for additional reinforcements, as the natives had become every day bolder and more enterprising, ever since their victory in Copaipo over Monroy and Miranda. Only a little before this, the Quillotans had contrived to massacre all the soldiers employed at the gold mines in their country, by the following stratagem. One day a neighbouring Indian brought a pot full of gold to Gonzalo Rios, the commandant at the mines, and told him that he had found a great quantity in a certain district of the country which he offered to point out. On this information, all were eager to proceed immediately to the place, that they might participate in the imaginary treasure. As they arrived at the place described in a tumultuary manner and entirely off their guard, they fell into an ambush, by which the whole party was slain, except their imprudent commander and one negro, both of whom saved their lives by the speed of their horses. About the same time the vessel which Valdivia had ordered to be built at the mouth of the river Chillan was burnt by the natives, together with the store-houses or arsenal which he had established in that place.

On receiving notice of the disaster which had taken place at the mines, Valdivia hastened to Quillota with a strong body of troops, and took revenge as far as he could on the Quillotans for the death of his soldiers; after which, he constructed a fort in their country in which he left a garrison for the protection of the people employed in the gold mines. Being soon afterwards reinforced by three hundred men from Peru, under the command of Francisco Villagran and Christoval Escobar, he made choice of a beautiful plain near the mouth of the river Coquimbo, at which place there is a very convenient natural harbour, near which he erected in 1544: a city which he named Serena, to serve as a place of arms to protect the northern part of Chili, and to secure the convoys and reinforcements which might come from Peru in that direction. This place is still known in geography by the name of Serena; but in Chili the native name of Coquimbo prevails, as is the case with most of the Spanish cities and towns in Chili.

In the ensuing year, 1545, Valdivia marched into the country of the Promaucians, with the view of extending his conquests to the southwards. Contemporary historians have not left an account of the events of this year, nor of any battles having been fought on this occasion; yet it is hardly to be supposed that this valiant tribe, who had so gloriously repulsed the armies of the Inca and of Almagro, would allow Valdivia to reduce their territory to subjection without a struggle. However this may have been, it is certain that he had the art to persuade the Promaucians to enter into an alliance with him against the other tribes of Chili; as ever since the Spanish armies in Chili have been assisted by Promaucian auxiliaries, owing to which the most rooted antipathy has been constantly entertained by the Araucanians against the remnant of the Promaucians. In the year 1546, Valdivia passed the river Maule, and reduced the natives to obedience from that river to the Itata. While encamped at a place named Quilacura, near the latter river, he was attacked one night by the natives, who destroyed many of his horses, and put him into imminent danger of a total defeat. His loss on this occasion must have been considerable; as he found it necessary to relinquish his plan of farther conquest, and to return to St Jago to wait reinforcements from Peru. As the expected reinforcements did not arrive, and Pastene, who had been sent into Peru to endeavour to procure recruits, brought news in 1547 of the civil war which then raged in Peru, Valdivia determined to go thither in person, expecting to reap some advantages from these revolutionary movements.

Valdivia sailed therefore with Pastene for Peru, taking with him a great quantity of gold, and left Francisco Villagran in charge of the government of Chili during his absence. Valdivia accordingly arrived in Peru, where he offered his services to the president De la Gasca, and acted with great reputation as quarter-master-general of his army in the war against Gonzalo Pizarro. The president was so much satisfied with the services which were rendered by Valdivia on this occasion, that, after the insurrection of Gonzalo was entirely subdued, he confirmed him in the office of governor of Chili, and sent him back to that kingdom with abundance of military stores, and with two ships filled with the soldiers who had served under Gonzalo in the late insurrection, glad of an opportunity of getting rid of so many seditious people for whom there was then no fit employment in Peru.

During the absence of Valdivia from Chili, Pedro de Hoz, who had been deprived of that share in the conquest and government which had been granted him by the court of Spain, and who had imprudently put himself under the power of his more successful rival, was accused of entering into secret practices for usurping the government. It is now unknown whether this accusation was well-founded, or if it were merely a pretence for getting rid of him; but, however this may have been, Villagran condemned him to be beheaded in 1548, either to please Valdivia by ridding him of a dangerous competitor, or perhaps in consequence of secret instructions for that purpose. About this time, the Copaipans killed forty Spaniards, who were proceeding in several separate detachments from Peru to Chili; and the Coquimbans, at the instigation of these northern neighbours, massacred all the inhabitants of the new city of Serena, and razed that place to the foundations. On this occasion Francisco Aguirre was sent into this part of Chili with a military force, to chastise the natives, and had several encounters with them with various success. In 1549, he rebuilt the city of Serena in a more commodious situation, and the inhabitants have ever since considered him as the founder of their city, many of the most distinguished inhabitants of which still boast of being his descendants.

After an incessant contest of nine years, attended by incredible fatigues, numerous dangers, and many reverses, Valdivia considered himself as solidly established in the dominion of that portion of Chili which had formerly been under the authority of the Incas. He accordingly distributed the territory among his followers in repartimientos, assigning a considerable portion of land with all its native inhabitants to each of his followers in proportion to their rank and services, under the denomination of commanderies, according to the baneful system of feudalism then prevalent in Europe. Having thus quieted the restless ambition and mutinous spirit of his soldiers, he advanced towards the south to extend his conquests, accompanied by a respectable force both of Spanish and Promaucians. After a march of 250 miles, during which he encountered few obstacles of any moment, he arrived at the Bay of Penco, now generally called the Bay of Conception, which had been already explored by Pastene during his voyage of discovery formerly mentioned; and near that excellent bay he laid the foundation of the third city in Chili, on the 5th of October 1550, to which he gave the name of Conception.