In 1951 he was elected national representative for young members. In 1958 he was elected deputy for the district of Rieti and Umbria. He served as minister for Foreign Affairs (1979-1980), Finance (1978-1979), Instruction, Industry, State trades, and Mail and Telecommunications.
He was also the third President of the European Commission from 1970 to 1972.
The "Malfatti Commission" began as the integration process was relaunched: the European Commission adopting a financial framework and competing the single market. There was also the beginnings of political cooperation, monetary cooperation and of enlargement as talks opened with Denmark, Ireland, Norway and the United Kingdom.
He resigned from this post in 1972 to run for office in Italy. In the 1980s he was chief of the Italian delegation in the European Parliament.
Politically close to Aldo Moro"s lobby, Malfatti was among the participants in Bilderberg meetings
He was an important member of the governing council of Democrazia Cristiana (the Christian Democratic party) in which he became chief of political bureau, and covered several institutional charges. In Democrazia Cristiana, he was a member of Dossetti"s lobby, together with Amintore Fanfani, Aldo Moro, and Giorgio Louisiana Pira.