The world number two came through a tight opening set by dominating the tiebreaker before finishing off his victory amid a smattering of jeers from the crowd.
The Serb lost to Rafael Nadal in last week's Madrid semi-finals, but his quick start in the Italian capital was just the tonic for Djokovic, who has never failed to reach the last eight in Rome.
In a shock to Maria Sharapova, the French tennis federation refused to grant the five-time Grand Slam winner and twice Roland Garros champion a wild card to either the main draw or qualifying.
The snub means the 30-year-old will not be in Paris for the clay major, although she could earn a place in the Wimbledon main draw by reaching the semi-finals in Rome.
British fifth seed Johanna Konta reached the third round with a crushing 6-3, 6-0 win over Yulia Putintseva.
Australian Daria Gavrilova beat former finalist and 10th seed Madison Keys 2-6, 7-5, 7-5, while Dutch 15th seed Kiki Bertens put out Monica Niculescu of Romania 2-6, 6-2, 6-1.