The world number one, bidding to equal Roger Federer's record of six titles at the season-ending event, brushed aside fifth seed Rublev 6-3, 6-2 to secure his 50th match win of the year.
Djokovic, thanks to successive straight-sets victories, has wrapped up top spot in the Green Group.
"I served well (and) that helped tremendously," Djokovic said. "I wanted to put him out of his comfort zone, taking away the time and mix up the pace. It was a great performance overall."
Norway's Casper Ruud plays British alternate Cameron Norrie later in the day.
The 34-year-old Djokovic is looking to cap off a remarkable year which saw him only just miss out on completing a calendar Grand Slam with defeat by Daniil Medvedev in the US Open final.
He plays Norrie in his last round-robin match on Friday.
A rematch with second-ranked Medvedev in the final in Italy is still a possibility, with the Russian reigning champion sitting top of the Red Group.
Djokovic is bidding for back-to-back titles after returning to action earlier this month with success in the Paris Masters, beating Medvedev in the final.
The Serb has not won the ATP Finals since 2015, losing finals in 2016 and 2018 to Andy Murray and Alexander Zverev respectively, while also falling in an epic last-four clash with Dominic Thiem last year.
The 20-time Grand Slam champion was far too strong for Rublev, though, serving 14 aces and hitting 19 winners past his overpowered opponent.
He broke twice in each set of a match which lasted just 69 minutes.
"Winning the first set, I put additional pressure on him, and I started to maybe play more consistently from the back of the court," Djokovic added.
Earlier, Norrie replaced Stefanos Tsitsipas in the draw after the Greek star pulled out with an elbow injury.
The world number four had refused to comment on the problem after his opening loss to Rublev, but admitted on Wednesday the injury which forced him to retire from his first match in Paris was still hampering him.
"I have taken the very difficult decision to retire from the 2021 Finals due to my elbow injury, which has been bothering me for a couple of weeks now," Tsitsipas said.
"It's a very difficult decision from my side."
Djokovic's win leaves Norrie with an outside chance of making the semis despite playing a match fewer than his rivals.
Italian youngster Jannik Sinner is in a similar position in the other group, after replacing the injured Matteo Berrettini and then seeing off Hubert Hurkacz on Tuesday.