It was late in the third quarter when the injury occurred, with the Pelicans trailing 84-81, as Williamson pushed the ball in transition before sharply pulling up, holding his right hamstring.
He had 26 points on 10-of-12 shooting, adding seven assists and six rebounds in his 28 minutes before the incident, with the 76ers taking the fourth period 36-30 following his departure.
Speaking after the game, Pelicans head coach Willie Green confirmed the injury as a right hamstring strain.
"It was right at a pivotal moment in the game," he said. "We'll get some imaging and look at him and hopefully he's okay. It was a tough loss for us."
Williamson has played in 28 of the Pelicans' 37 games up to this point after missing the entire 2021-22 season, and had rediscovered his best form in December.
He averaged 29.8 points, 7.5 rebounds and 5.1 assists per game while shooting 61.3 per cent from the field during his 12 games in December, picking up the slack while team-mate Brandon Ingram has been sidelined.
Joel Embiid ended up as the star of the 76ers' win, scoring a game-high 42 points with 11 rebounds and five assists.