Mattarella, 73, was elected by lawmakers on Saturday to succeed the elderly Giorgio Napolitano.
A Sicilian who is closely associated with the fight against organised crime, he becomes Italy's 12th president since the country became a Republic after World War Two.
His election has been seen as a political coup for Italy's Prime Minister Matteo Renzi.
The youthful, centre-left prime minister had backed Mattarella despite opposition from opposition leader and former premier Silvio Berlusconi.
Renzi's candidate comfortably carried the vote with 665 of the votes cast in a 1,009-member electoral college.
The new president was until now little known to ordinary Italians. But the white-haired former academic has long been a respected figure in political circles after a 25-year parliamentary career and several stints as minister in governments of the left and right.
He entered politics after his elder brother, who was president of the region of Sicily, was murdered by the Mafia in 1980.
Mattarella is also seen as a foe of Berlusconi, having once resigned from government over a media law he and other ministers regarded as overly favourable to the tycoon's television interests.
The new president is now being a member of Renzi's Democratic Party (PD) having started his career as a Christian Democrat.
The presidency in Italy is a largely ceremonial role but the holder of the office can play a significant role at times of political crises, which have been a regular feature of Italian life for the last half century.