PUC-SP was founded in 1946, from the union of the Faculty of Philosophy, Sciences, and Letters of São Bento (founded in 1908) and the Faculty of Law of São Paulo. Added to them, but with independent financial administrative structures, were four other Church institutions. Time at the Catholic University of São Paulo, whose mission was to train Catholic leaders and the children of the São Paulo elite.
At the beginning of the following year, Pope Pius XII granted the title of Pontifical to the Catholic University and appointed Cardinal Dom Carlos Carmelo de Vasconcelos Mota as the first Grand Chancellor of the institution. Also, the archbishop of São Paulo, Cardinal Mota was the founder and one of the main creators of PUC-SP.
At the end of the 1960s, PUC-SP began to develop what would be its essence: academic quality linked to social concern. In 1969, the University created the country's first organized graduate course. In 1971, another bold academic proposal: the emergence of the Basic Cycle of Human Sciences. Academically, the institution started to function as a true university by valuing and considering teaching, research, and extension inseparable.
In 1973 the Faculty of Medicine and the Faculty of Nursing of Sorocaba, both founded in 1951 and pioneered as faculties in the health field outside the axis of large capitals, were incorporated into PUC-SP, creating the Sorocaba campus.
The University's bold attitudes put it at the forefront of the fight against the military dictatorship as a defender of freedom, rights, and democracy. In the 1970s, the University hired professors who had left the public institutions in which they worked, who were compulsorily retired by the military. They became part of the intellectual staff at PUC-SP, such as Florestan Fernandes, Octavio Ianni, Bento Prado Jr., José Arthur Gianotti.
In July 1977, PUC-SP hosted the 29th meeting of the Brazilian Society for the Progress of Science (SBPC), which had been banned by the government from taking place at public universities. Months later, on 9/22, students performed an act in front of Tuca to celebrate the 3rd National Student Meeting, which was also banned by the military; the students also celebrated the reorganization of the student movement and the National Students Union (UNE), which operated in hiding. It was the trigger: Military Police troops, personally led by the Secretary of Public Security Erasmo Dias, invaded the Monte Alegre campus. Police officers dropped bombs on protesters and arrested teachers, students, and staff. The invasion caused a lot of damage to the University.