Antonio Paolucci has been art superintendent in Venice, head of Florence museums and Italy's culture minister in 1995-96.
Paolucci, 68, has also served as the government commissioner overseeing the restoration of the Basilica of St. Francis in Assisi following a 1997 earthquake.
He replaces Francesco Buranelli, who was named secretary of a Vatican cultural office.
The Vatican museums gather hundreds of artworks from painters including Michelangelo and Raphael. The Sistine Chapel is the last stop on a tour of the museums.
Last year, 4.2 million people visited the Vatican museums.