Embiid suffered a left shoulder sprain after colliding with Cleveland centre Ante Zizic with 49 seconds left in the opening quarter.
Still smarting from the collision, the seven-foot Embiid grimaced as he missed both free throw attempts. He did not stick around and went straight to the locker room.
Embiid briefly returned to the bench in the second quarter before being taken out of the game for good at halftime. He is expected to be examined by team doctors on Thursday to determine the extent of the problem.
Sixers coach Brett Brown said he was "unsure" whether Embiid would play in Thursday's home game against the New York Knicks.
"I'm really sort of a prisoner to the medical people's information," Brown said. "I haven't checked in. I'm unsure, I really am unsure."
Embiid's injury is the latest for Philadelphia, who are without Ben Simmons after the all-star guard was injured during Saturday's 119-98 loss in Milwaukee. Simmons has a nerve problem in his lower back.
Earlier on Wednesday, the NBA fined Embiid $25,000 for making an obscene gesture on the court and using profanity during a TV interview.
Those incidents took place during Philadelphia's 129-112 win over Atlanta on Monday, a game in which Embiid scored a career-high 49 points.
Kevin Love sank a three-pointer to extend Cleveland's lead to 70-50 midway into the third quarter. But the Sixers quickly answered with 11 straight points.
Milton and Al Horford made baskets from beyond the arc to cut the Cavaliers' lead to 85-80 with just over nine minutes left in the game.
In San Antonio, Luka Doncic scored 26 points, dished out 14 assists and grabbed 10 rebounds as the Dallas Mavericks hold off the San Antonio Spurs for a 109-103 win.
Kristaps Porzingis led Dallas with 28 points. Tim Hardaway added 17 points and Dorian Finney-Smith tallied 14 for the Mavericks.
DeMar DeRozan led San Antonio with 27 points.
Elsewhere, Bradley Beal scored 30 points and combined with Jerome Robinson for the go-ahead three-pointer with nine seconds remaining as the Washington Wizards pulled out a 110-106 win over the Brooklyn Nets.
Also, Russell Westbrook and James Harden connected for 63 points, allowing the Houston Rockets to stretch their winning streak to five games with a 140-112 victory over the Memphis Grizzlies.