Napolitano, who will turn 90 in June, said he had reached the age when it was difficult to do his job and was therefore ready to resign his high post, as the constitution allowed. The octogenarian added the decision to step down was his and his alone.
Speaking about Italy's future, the outgoing president said his resignation would be in the interest of the nation, and urged the country's leadership to be responsible about picking his successor.
Prime Minister Matteo Renzi, who assumed his post less than a year ago, will be the one in charge until a new president is elected.
Napolitano has been the first president in Italy's history who has ever been re-elected for a second term, although he made it clear quite soon after his second swearing-in in 2013 that he was considering an early departure. But he stressed he was only doing it out of a feeling of responsibility before his country.