He becomes the first man to win all nine Masters title, no other player has more than seven.
Novak Djokovic (SRB) returns a shot against Roger Federer (SUI) during the finals in the Western and Southern tennis open at Lindner Family Tennis Center.
"Thank you for letting me win once in Cincinnati", Djokovic said to Federer.
Djokovic has the fourth highest number of Grand Slams, under his belt, after Federer, Nadal, and Sampras.
"That's what the headline should be about - this is such an awesome accomplishment", Federer said.
Federer was making too many errors and Djokovic refused to allow him a way back, the Swiss spraying a forehand wide under pressure after being pushed back to spark exuberant celebrations from 13-time major victor and history maker.
Federer's streak of 100 straight unbroken service games in Cincy was ended by Djokovic in the seventh game of the first set. "It's the first time I get to stand with a winning trophy in Cincinnati".
"But I don't even want to look for reasons why it happened", he added.
Novak Djokovic celebrates after his first win in Cincinnati. This (effort) was not good enough.
But Federer started the second set the strongest, racing into a 2-0 lead before Djokovic fought back to level at 2-2.
The Serb now leads Federer 24-22 and has won their last three encounters.
The pair had not played since the 2016 Australian Open semi-finals more than two and a half years ago.
Victory also completes an incredible sweep for Djokovic as he has now won all Masters events, all Grand Slams and all World Tour Finals.
His first classy act came just after match point when Federer smiled and hugged Djokovic at the net, offering some nice words of congratulations.