Djokovic, who went vacant in five previous Cincinnati finals, defeated seven-time winner Roger Federer 6-4, 6-4 in the final.
The former number one in the world became the first man to win all nine of the ATP Masters 1000 events in the current configuration of the elite series.
Federer lost a final in the US Open hard court
For the first time.
"I've played five finals before (and here) and I lost most of those finals for this great man, Roger … thank you for letting me win here in Cincinnati," Djokovic joked.
"This is a dream come true," Djokovic said.
"I finally won Cincinnati after six finals, some against the best ever, Roger."
Federer, a winner of the Grand Slam, said his match was not sharp, but he did not want to diminish the performance of Djokovic.
"Novak is a great champion," said Federer.
"This is about making history."
Federer's streak of 100 straight unbroken service games at Cincy was terminated by Djokovic in the seventh game of the first set.
The 37-year-old Swiss had striven for a 99th career trophy, but could not cross the line, partly because of four double errors at the most inconvenient moments, but he also said his return match was missing.
"It was definitely not my best day on return – it was just terrible," said Federer.
"Missing every second serve in advance, I do not know what that was about.
"But I do not even want to look at why it happened," he added.
"Novak completely deserved to win today, which was not good enough.
"Good week, but I'm glad it's over and I have to rest," Federer added, his eye on the US Open, starting in New York in eight days.
Djokovic claimed the opening set in 37 minutes and came back from an early break in the second to rework his old rival while playing for the 46th time.
– & # 39; Great feeling & # 39; –
The Serb now leads Federer 24-22 and has won their last three encounters.
The duo played more than two and a half years ago since the semi-final of the Australian Open in 2016.
Wimbledon champion Djokovic claimed his Masters record at his first match point and now goes to the US Open as a title favorite after a series of gap seasons and an elbow injury for which surgery was needed.
"It's a great feeling, it's been a few difficult months for me with an injury and then winning Wimbledon and Cincinnati," Djokovic said. Federer started the game with three aces in the opening game and added a pair of love games for a 3-2 lead.
But it began to unravel because the Swiss doubled to reach a breaking point and drop while Djokovic led 4-3.
Djokovic took advantage of a 5-3 lead and closed the set after 37 minutes.
Federer broke for a 2-0 lead in the second set, but immediately gave the return when he made a mistake twice and gave Djokovic a breaking point that promptly converted the Serb.
Djokovic broke again to lead 4-3, and after Federer had held to close the opening to 4-5, Djokovic ended the afternoon in the next game at his first match point.