Djokovic, who is looking to win his 33rd ATP World Tour Masters 1000 crown this week in the French capital, will return to the summit of men's professional tennis on Monday nearly two years to the day since he completed his 223rd and most recent week in top spot.
The Spaniard is playing his first match since retiring with a knee injury in the semis of the US Open nearly two months ago, so will be fresh, even if his fitness is untested in the heat of competition.
Federer, Nadal and Djokovic have gathered 729 weeks at the world number 1 position so far and this is unlikely to change anytime soon as they are still in front of all the other rivals on the Tour!
"But I haven't been really reflecting on that and I haven't been really focusing on that too much because it's the middle of the week. I didn't want to play there at that time", said the 20-time grand slam champion. Nishikori beat Frenchman Adrian Mannarino 7-5, 6-4 while Isner battled past Mikhail Kukushkin 6-3, 6-7 (2), 7-6 (1).
It helped him to maintain the remarkable spell of form that has seen him rise from number 22 in June to the top of the game again.
He beat Djokovic here at the equivalent stage two years ago and also at this year's Queen's final before Wimbledon.
The four-time Paris champion, who next faces Marin Cilic in the last eight on Friday, was guaranteed a return to the ranking summit when Nadal withdrew from Paris with an abdominal injury on Wednesday.
The Serb won his last 16 tie with Damir Dzumhur after the Bosnian was forced to retire trailing 6-1, 2-1 at Bercy. At the U.S. Open, he retired during his match against Juan Martin del Potro.
Serbian tennis player Novak Djokovic in the tournament ATP 1000 in Paris to guarantee his return to the first line of a world rating.
"I served better than him at important moments".
Yet his opponent, Milos Raonic, pulled out because of injury, leaving Federer to think that it had actually turned out to be a blessing in disguise.
John Isner's hopes of also making the London finals received a potentially fatal blow when he was beaten 6-4 6-7 (9) 7-6 (8) in by rising Russian Karen Khachanov. But it is Djokovic who will be top dog when the latest ATP rankings appear on Monday, irrespective of his fate in the French capital this week. The American got past lucky loser Malek Jaziri, but will now run into Dominic Thiem.
Fourth-seeded German Alexander Zverev booked his place in the next round with a 6-4 6-4 win over Frances Tiafoe.