The midfielder, starting his second game in six days, pulled up while off the ball and soon sit down on the pitch.
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.
Chelsea vs Tottenham LIVE: Latest score and updates
Arsenal dealt new injury worry as 'slight' Calafiori issue is confirmed
Arsenal player ratings: Two 8/10s as 'colossal' defender scores 9/10
Rediscover your adventurous side on an exotic getaway
Maddison impressed in the first half at Stamford Bridge, but was forced off with less than four minutes of the second half played.