The Serbian, 31, beat Rafael Nadal’s semi-final conqueror 6-3 6-4 in one hour 32 minutes to earn a record-equalling 33rd Masters 1000 title.
Djokovic raced into a 3-0 lead in the opening set after breaking the 20-year-old Greek in the second game.
And he broke in the ninth game of the second set to ensure he didn’t drop a set all tournament.
Djokovic’s 74th Tour title came after having made just one quarter-final in three tournaments since lifting the trophy at the Australian Open for a seventh time.
“This is a very important win for me, especially for my confidence,” Djokovic told Sky Sports. “I wasn’t playing my best tennis after the Australian Open so I was looking to regain momentum. I played some of my best tennis here.”
On his opponent, he added: “I needed to step up, Stefanos is very talented. He beat Rafa yesterday, he had a late night and he wasn’t as dynamic in his movement and that was probably due to his long match.”
Tsitsipas, who beat Roger Federer at the Australian Open, has had a superb season and in addition to his win over Nadal, had won the previous match against Djokovic at the Rogers Cup in Toronto last August.
But he struggled to match the 15-time Grand Slam champion, who had superior energy after overcoming Austrian Dominic Thiem in the semi-finals.
Tsitsipas, who saved three match points, said of Djokovic: “It’s inspiring what you do, simply amazing. You deserve it.
“You had a great week. It was also a great one for me, with good memories and good crowd support.”
Djokovic, who matched Nadal’s record for Masters 1000 triumphs, will hold all four Grand Slam titles if he goes on to claim a second French Open title next month.