He was initially near to Mario Scelba's wing within DC, but later moved to Giulio Andreotti's current, becoming one of the latter's frontmen in Rome alongside Amerigo Petrucci and Franco Evangelisti. In 1968 he was elected into the Italian Senate, and was confirmed until 1985. Signorello was Minister of Tourism, Sport and Spectales in 1973-1974, Minister of Merchant Marine in 1980 (replacing Evangelisti) and then again Minister of Tourism in three consecutive cabinets from 1980 to August 1983.
Signorello was elected as Mayor of Rome in May 1985, after years of Communist government of the city, remaining in charge until 1988. He abandoned the political activity in 1989.