The school was established by the friars of the Order of the Preachers as the Colegio de Santo Tomas de Nuestra Señora de Santissimo Rosario in 1611.
In 1645, It was raised to the status of a university by Pope Innocent X.
The university was graced with the following titles: “Royal” by King Charles III of Spain, 1785; “Pontifical” by Pope Leo XIII, 1902; and “Catholic University of the Philippines”by Pope Pius XII, 1947.
It was destroyed during the Second World War. It moved out of Intramuros in 1945 to Sampaloc, Manila, where its present campus now stands.
The office building that occupies the site was constructed in the 1960s.