The midfielder, starting his second game in six days, pulled up while off the ball and soon sat down on the pitch.
After talking to his team-mates, it was quickly decided that Maddison could not continue.
Conor Gallagher, former Blues player, was brought on as his replacement to a chorus of boos from the home side.
It’s a huge blow for Spurs and Maddison, who was the standout performer against Coventry on Monday evening in his first first for 17 months by scoring a stunning opener from distance.
Maddison was a doubt heading into the derby at west London, having not been able to train in the three days after the game.
Roberto De Zerbi played down the chances of a Maddison start at his pre-match press conference on Friday, only for the England man to get the nod on Saturday evening.
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Maddison impressed in the first half at Stamford Bridge, but was forced off with less than four minutes of the second half played.