The Celtics were in control of the game when Irving hurt the knee with about five minutes left in the second quarter while attempting to defend Garrett Temple at the top of the key.
The Clippers outscored the Celtics 75-44 after Irving left the game, coming back from 28 points down to win 123-112.
It was the largest comeback in the NBA in the past two seasons and the largest in Clippers history. It was the biggest blown lead by a Celtics squad since Dec. 5, 2003.
Two nights earlier, Boston gave up an 18-point lead to the Los Angeles Lakers at TD Garden.
Celtics coach Brad Stevens said Irving’s knee appeared to “buckle” and that the 26-year-old will undergo more tests on it Sunday.
But Stevens said the injury wasn’t to blame for his team’s collapse.
“There’s no excuses,” Stevens told NBC Sports Boston. “Those things happen and we all have to pick up for that. So I’ll go back and figure out what I can do better, what we can do better, and we’ll go from there.”