Djokovic then held at love and again in the ninth game to claim the set from 0-30 when Raonic netted a forehand.
The H2H record does not look good for Raonic here as he has lost on all 10 occasions he has met Djokovic and has won just two of the 26 sets they have contested.
The Canadian continued his ruthless form on the quick hard courts of NY, facing just one break point during the match to beat Tsitsipas for the second time in 2020.
Taming his strokes nicely, Djokovic had the edge in the shortest and mid-range exchanges, gathering momentum ahead of the decider where he was the favorite.
The World No.1 has now won 22 straight matches to start the season and 25 overall.
Djokovic, who has been struggling with a neck injury and received assistance from a tournament physio in the second set, held on to prevail in the third set as his opponent forced the match into a tiebreak.
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On this occasion, the eighth seed saved a break point to consolidate for a 5-3 lead and comfortably served the set out two games later. Milos held at 30 in the first game with a forehand victor, wasting a break chance in the next one and forging a 2-1 advantage with a service victor. But he couldn't serve out the match and was blasted in the tiebreaker.
Raonic has found a rich vein of form since tennis has resumed in 2020, and he is looking like a potential dark horse at the US Open.
"I'm moving much better than I definitely have in recent years", Raonic said. "Maybe it's been a long time, and I think that's putting me in better position so I'm able to be more effective and more aggressive earlier".
"I'm feeling good about my tennis".
The Western & Southern Open is seen as a great way for the US Open participants to get a feel of the hardcourt. The Canadian secured another break in game six following Novak's double fault, sealing the opener with an ace in game seven for a 6-1 after 30 minutes. I still have that sharpness and motivation in my everyday routines. "I was waiting and waiting and then I realized I was the one who was going to have to take the first step".
Djokovic also tied Rafael Nadal with 35 Masters 1000 titles by winning the Western & Southern Open for the second time in three years. The Serb took down Milos Raonic 1-6, 6-3, 6-4 in two hours, staying undefeated in 2020 and delivering the 11th triumph over the Canadian in as many encounters.