After gathering a defensive rebound off a shot from 76ers center Joel Embiid, Williamson tried to quickly push the ball up court, but as soon as he crossed the half-court line, Williamson pulled up and dribbled to the left corner. He then handed the ball off to teammate Dyson Daniels while grabbing at his right leg.
After a missed shot, Pelicans center Jonas Valanciunas fouled Philadelphia's Tyrese Maxey on a fast-break layup and Williamson checked out of the game with 24.1 seconds left in the third quarter. The Pelicans later announced he would not return midway through the fourth.
Following the game, Pelicans coach Willie Green said the only update he had on the injury was that it was a right hamstring strain.
"It was right at a pivotal moment in the game," Green said. "We'll get some imaging and look at him and hopefully he's OK. It was a tough loss for us."
The Pelicans on Tuesday ruled Williamson out for Wednesday night's home game against the Houston Rockets.
Williamson had 26 points, seven assists and six rebounds on 10-of-12 shooting when he checked out. He previously missed two games because of a lower back/right hip contusion, three games because of a right foot contusion and three games while in the health and safety protocols.
New Orleans is also without Brandon Ingram, who has played in only 15 games this season and has not played since Nov. 25 because of a left big toe contusion. Ingram was also ruled out for Wednesday's game.
After the Rockets, the Pelicans host the Brooklyn Nets on Friday.