The world number one said he played a "perfect set" to race through the opener, before coming from a break down in the second to earn a 6-0 7-6 (7-5) victory in Sunday's final.
Djokovic made it a record-extending 38th Masters 1000 title in what was his 55th final at this level, and it was his sixth triumph at this event in the Italian capital.
At 34 years, 11 months and 23 days old, Djokovic is 10 days older than the previous oldest Rome champion, Rafael Nadal, who took the title last year.
He boosted his head-to-head record to 7-2 against Greek star Tsitsipas, winning their last six matches and all five they have contested on clay, including last year's French Open final where Djokovic came from two sets behind to scoop the grand slam. This victory clearly augurs well for Djokovic's upcoming title defence in Paris.
Djokovic broke serve to love in the opening game, Tsitsipas swatting a volley into the net to hand over the early advantage and set the tone for a wildly one-sided set.
Tsitsipas broke to lead 3-1 in the second set and he served for it at 5-3 but was broken to 15, sending a forehand wide on game point. The tie-break that soon followed was hard fought, with Tsitsipas looping a backhand long on match point as Serbian Djokovic earned the trophy once again.
Reflecting on his fast start, and his first title of 2022, Djokovic said on Amazon Prime: "I pleasantly surprised myself, I can say, even though I had a clear game plan and strategy coming into the match. I knew what to expect from the other side so I knew what I had to do, but I did play a perfect set, no doubt about it.
"After that it was a little bit tight, the beginning of the second for me. He used it, and at this level one or two points can turn a match around and he was back in the game. At 4-1 up for him and 30-40, the match could have easily gone into a third set, but I somehow managed to find the right shots at the right time to come back in the game, and the tie-breaker, I guess I was just an inch better, maybe calmer, and it was a tight tie-break for both of us."
Ahead of the French Open, which gets under way next Sunday, Djokovic is feeling in great shape for his title defence. Having missed the Australian Open in January in a deportation drama, Djokovic will head to Paris as a major rival to teenage sensation Carlos Alcaraz.
Should Djokovic triumph at Roland Garros, he would match Nadal's men's record of 21 grand slams.
"I've been building my form in the last couple of weeks and like the previous years I knew that my best shape on clay was usually coming around Rome time," Djokovic said.
"So it couldn't be a better time, coming into Roland Garros with a title at this wonderful tournament. I'm going to Paris with a lot of confidence."