Forest owner Evangelos Marinakis left his seat during the match at the City Ground in an ominous sign for the Australian, and his fate was confirmed shortly after full-time.
"Nottingham Forest Football Club can confirm that after a series of disappointing results and performances, Ange Postecoglou has been relieved of his duties as head coach with immediate effect," the club posted on X.
"The club will make no further comment at this time."
It is the shortest managerial reign of any permanent Premier League manager to leave a club during the season.
Postecoglou was only appointed on September 9th, but has failed to win a single match in his eight games in charge in all competitions.
Forest collected just one point from his five Premier League matches at the helm, leaving the side one point above the relegation zone in 17th spot.
The club are now on the hunt for a third manager this season after Nuno Espirito Santo was dismissed last month.
Postecoglou, sacked by Tottenham in June, was defiant at his pre-match press conference on Friday, saying if he is given time at a club, it always ends "with me and a trophy."
Last season, he won the Europa League with Tottenham, in his second season in charge, though a terrible league campaign cost him his job.
Former Burnley and Everton manager Sean Dyche is reportedly in the frame to be the new boss at Forest.
The Chelsea match was an unhappy final chapter in a miserable reign for Postecoglou, 60.
The home side started brightly against Chelsea but failed to take their chances.
Teenager Josh Acheampong headed the visitors ahead early in the second half before Pedro Neto curled home from a free-kick.
Captain Reece James made it 3-0 late on to lift Chelsea into fourth spot in the table ahead of the 16:00 CET kick-offs.
Read a full match report from Chelsea's win here.
Chelsea were without a long list of first-team players, including Cole Palmer, Benoit Badiashile and Enzo Fernandez, while Moises Caicedo started the game on the bench.
But ultimately, they were too strong for Forest.
The visitors took the lead when Neto sent in an inviting cross for defender Acheampong, who headed home for his first senior goal in the 49th minute.
Three minutes later, Chelsea doubled their lead when Neto curled his free-kick around the wall of red shirts, past the despairing dive of Matz Sels.
Nikola Milenkovic and substitute Igor Jesus failed to take chances for Forest, and James scored late to make it 3-0 on his 200th appearance for the club.
That sparked a mass evacuation from the City Ground, leaving Postecoglou pensive on the touchline.