Tsitsipas, who will break into the top 10 for the first time Monday, held firm up to 4-4 in the second set before the 37-year-old Federer switched gears to take the decisive break and serve to win the match.
Roger Federer could win the 100th title of his career at the Dubai Championships.
It was only the second time the pair had met, with Tsitsipas beating Federer in four sets in the Australian Open last 16 in January.
"I'm delighted. It's great to win my eighth here in Dubai and in combination with my 100th singles title", said Federer following his victory, BBC Sport reported. "I got off on a flyer in the beginning and never looked back", said Federer, who landed 76 per cent of his first serves and won 83 per cent of those points. "I hadn't played since Australia". I'm proud about the things I have done and tonight was a very special evening, playing Stefanos and seeing the future coming up in the tennis game, it's part of this whole journey. I'll be happy with 100 wins! "Tennis is in good hands, whether I'm there or not".
So it seemed like that he is not anxious about his loss and he is privileged to play against his idol and joyfully had an eye on him while Federer lifting his 100th title. I think what Jimmy did was an unbelievable achievement.
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Kyrgios, whose run to the final included a bout with food poisoning and three-set victories over top-seeded Spaniard Rafael Nadal, Switzerland's Stan Wawrinka and third-seeded American John Isner, struck 13 aces against Zverev and converted three service breaks.
Fourth seed Federer - complete with his ponytail - dropped just one set during the tournament, but it was not all plain sailing as he was troubled by a back injury in a fourth-round victory over Feliciano Lopez.
World number 11 Tsitsipas was Federer's 50th different final opponent and the 25th different nationality.
"If I reach milestones like this along the way, it's wonderful".
The errant forehand into the middle of the net gave Federer a 5-4 lead and gave him a chance to serve out the match after the changeover.