The result means that Liverpool, who thrashed Crystal Palace on Wednesday, have clinched a first-ever Premier League title and a first in England's top flight in 30 years as Man City can no longer mathematically catch the leaders, whom they trail by 23 points.
After the match, Man City boss Pep Guardiola said: "Big congratulations to Liverpool for this great season and the title they won. We have a lot to play for this season, but of course we will try to be close to Liverpool next season.
"We were not consistent like the previous season. They had incredible focus and played every game like it was the last game. In the beginning we didn't play that way."
Manchester City dominated possession in the opening half-hour, but couldn't find a goal as the hosts continued to grow into the match.
A mixup at midfield by the City defence allowed Pulisic to rush on to a loose ball, with the U.S. international charging in on goal and calmly slotting past Ederson to put Chelsea ahead in the 36th minute.
The goal was Pulisic's second in as many games and seventh in the Premier League this season as Chelsea took a 1-0 lead into half-time.
Pulisic looked to have had his second on the night to restore Chelsea's lead, but an incredible defensive effort from a sliding Kyle Walker kept the ball from crossing the goalline.
More goalline heroics from Ederson and the City defence looked to have kept Chelsea from taking the lead, but VAR intervened to award a penalty to Chelsea for handball on Fernandinho, with Willian stepping up to dispatch the spot kick for 2-1.
Fernandinho was shown a straight red for having swatted Tammy Abraham's goal-bound shot away on the goalline and Man City could not find a way back into the match as they finished down a man.
Chelsea boss Frank Lampard, who won three Premier League titles as a player at Stamford Bridge, congratulated Liverpool in a news conference and said it was up to other clubs to match them and Guardiola's City.
"I think for the last three seasons, themselves [Liverpool] and City have been out on their own pretty much, and that's a lot of work," he said.
"It's a gap that we want to try and breach, we want to move up towards -- they are two of the best teams in the world. Again, credit to Liverpool for what they've done."
Title-implications aside, the win was also a massive boost to Chelsea's quest to finish in the Champions League places, solidifying the team's hold on fourth place in the table with 54 points.