UC Chile was founded on June 21, 1888, by the Archbishop of Santiago, to offer training in traditional professions (law) and in technological and practical fields such as business, accounting, chemistry, and electricity.

Its first chancellor was Monsignor Joaquín Larraín Gandarillas, and at the very beginning, the university only taught two subjects, law and mathematics.

On February 11, 1930, Pope Pius XI declared it a pontifical university, and in 1931 it was granted full academic autonomy by the Chilean government.

Other UC activities are a Sports Club, and a Clinical Hospital dependent on the Faculty of Medicine.

Two of its most important alumni are the Jesuit Saint Alberto Hurtado and Eduardo Frei Montalva, a Chilean president.

In April 2013, UC Chile and the University of Notre Dame also signed a memorandum of understanding to strengthen scholarly engagement and expand their long-standing relationships.