In 1551 Pedro de Valdivia founded the original city of Concepción north of where it is today, near Penco (indeed, Conce's inhabitants are still known as Penquistas). Over the next few centuries the city was repeatedly besieged during the Spanish-Mapuche war, attacked by British and Dutch pirates and devastated by earthquakes in 1730 and 1751. But the colonizing residents stuck to their guns, and Concepción eventually became one of the Spanish empire's southernmost fortified outposts.

After independence, Concepción's isolation from Santiago, coupled with the presence of lignite (brown coal) near Lota, a coastal town south of Concepción, fomented an autonomous industrial tradition. The export of wheat for the California gold-rush market further spurred the area's economic growth.

During the early 1970s the city was a bulwark of support for Marxist President Salvador Allende and his Unidad Popular party, and it suffered more than other regions under the military dictatorship of 1973 to 1990.