Educated at the Catholic University of the Sacred Heart in Milan, Scalfaro worked as a prosecuting attorney. A member of the Christian Democrats (Italian Popular Party) (Democrazia Cristiana; DC), he was first elected to the Chamber of Deputies in 1948 from Turin-Novara-Vercelli, and he retained the seat for the following four and a half decades. He held a number of positions in the DC and was secretary and vice-chairman of its parliamentary group and a member of its National Council. He also held leadership positions in the Chamber of Deputies; he was elected chair of the legislative body only a month before being chosen as president. Beginning in the 1950s, Scalfaro served in several governments as an undersecretary of various ministries and as the minister of transport and civil aviation, education, and the interior. In 1987 he was unsuccessful in an attempt to form a government.

Parliamentary members elected Scalfaro, a compromise candidate, to the largely ceremonial post of president on May 25, 1992, after almost two weeks of unsuccessful attempts to reach agreement. The period of his presidency was marked by continuing political instability and a major realignment of political groups in which the DC, long dominant in Italy, disappeared as a separate party. At the end of his term Scalfaro was appointed senator for life.