With the Royal Ordinance of Intendants of 1784, the Corregimiento of San Miguel was suppressed and Piura became one of the most prosperous partidos of the Intendancy of Trujillo, governed by a subdelegate. The census of Gil de Taboada (1790–1795) and the chronicles of Bishop Martínez Compañón portray a dominant mestizo society, with indigenous communities in Catacaos and Sechura, an urban Afro-Peruvian population and Creole landowning elites such as the Seminario, Fernald and Velásquez de Tineo families.

On November 13, 1741, in the middle of the War of Jenkins Ear, a British squadron commanded by Commodore George Anson took the port of Paita by surprise, sacked the pier and set fire to the town and its churches. The sailors desecrated the Mercedarian chapel and Anson stabbed the effigy of Our Lady of Las Mercedes, whose gash is still preserved; the image washed ashore unharmed the following day. The event consolidated her devotion, and centuries later she was declared Patroness of the Arms of Peru.

With no mineral veins, the viceregal economy of Piura revolved around the algarrobo groves for goat herding and their by-products, as studied by Susana Aldana Rivera. In the «soap vats» and tanneries to the north of the city — the first industrial district of Piura — tallow was rendered and goat hides were processed into famed «cordovans». The soap supplied Huancavelica and Potosí, and the cordovans were shipped to Callao and Panama by cabotage.

On November 11, 1587, Viceroy Conde del Villar ordered the definitive relocation to the lower basin of the Piura river; Captain Juan de Cadalso Salazar chose the wooded site of El Chilcal, in Tacalá. The formal founding was completed on August 15, 1588 with the solemn distribution of building lots and the constitution of the town council, with the original notarial act preserved. The site offered abundant fresh water, alluvial soils, a temperate microclimate sheltered by algarrobo trees and protection from the sea: it is today Piura.

Around 1572–1578 the population settled on the bay of Paita to benefit from maritime trade with Panama. The site lacked fresh water, which had to be brought by raft from Colán or the Chira river, and was extremely vulnerable: Francis Drake besieged it in 1579 and in 1587 Thomas Cavendish landed with artillery, sacked the royal storehouses and reduced the wooden-and-cane houses and churches to ashes, forcing a total evacuation.

Toward the end of 1534, by order of Diego de Almagro ratified by Pizarro, the town was relocated to the Alto Piura, at the site of Monte de los Padres, next to the lands of the cacique Señor de Piura (today district of La Matanza). It flourished there for four decades with a regular grid, a Main Square and a Main Church, as revealed by the excavations of the University of Piura and the Polytechnic University of Madrid. By 1570 the collapse of the water table, climate fluctuations and the «mal de ojos» (eye blight) made the settlement untenable.

On his third expedition, Francisco Pizarro established a camp in the Chira valley and founded the first European city of the South American Pacific at the Tallán village of Tangarará. Historiography debates its date — Maticorena proposed July 15 and Del Busto August 15, 1532, the officially adopted date — because the original founding act disappeared. Pizarro distributed building lots, planted the pillar of justice, instituted the first town council and left Sebastián de Benalcázar as lieutenant governor. The site proved unhealthy: malaria, heat and indigenous hostility forced its abandonment.