The Serbian flew to a 6-4 6-4 victory over his long-running rival to win the only Masters 1000 tournament he had not yet won.
Five years after winning his eighth different crown, the former number one in the world could claim the elusive ninth and final title of the set after losing five previous finals in Cincinnati – three for Federer.
Djokovic did not win a set in any of these defeats, but he took the first time this time.
The Swiss demanded an early breakthrough in the second, but a staggering service game and a rare double foul immediately brought the break back to his opponent.
Federer struggled with his footwork and failed to take advantage of Djokovic's second store, and opened the door to the Serb's decisive breakthrough at 4-3.
Djokovic kept his guts, sealed the victory on his first match point after only an hour and 25 minutes on the track.
Djokovic said after the game: "It is clearly a very special moment to be here for the first time with the winning trophy here in Cincinnati.
"The hard times I went through, it was a roller coaster ride in my career with injuries, taking time off and surgery earlier this year.
"This seems a bit unreal to be back at this level."
Will Novak Djokovic play at the US Open?
Djokovic will not only play at the US Open, but he is also the early favorite of the bookmakers to win 2/1 to win in New York.
The 31-year-old finished sixth for the tournament, with world top two Rafael Nadal and Federer respectively achieving the two best seedings.
Argentinian Juan Martin del Porto is placed third, while John Isner is the highest placed American in the men's selection at number 11.
Novak Djokovic fitness last
Djokovic finished his season in mid-2017 and withdrew from a Wimbledon quarterfinal against Tomas Berdych with a right elbow complaint to be operated later.
The Serb then revealed that he had dealt with the problem since the beginning of 2016, which means that when he returned to action at the Australian Open in 2018, he spent more than two years in his elbows problem.
The star was then forced to operate more on the problem after he lost to Hyeon Chung in Melbourne.
His world rankings began to plummet, but Djokovic has been completely fit ever since and reminded the tennis world of his talent by claiming his fourth Wimbledon title in July.
Added to his recent Masters flight, Djokovic now looks back on his very best and rightly the favorite for the US Open next week.