Less than five minutes into the game, a driving Fultz was cut off by Cavs rookie Isaac Okoro, and Fultz's left knee buckled without contact.
Fultz, the No. 1 pick in the 2017 NBA draft, writhed in pain on the floor for several minutes before he was helped into a wheelchair.
Fultz posted a tweet later Wednesday, writing in part, "God has a plan for me and I know that this adversity will only make me stronger in the end."
"I believe in my brothers on this team and we have so much more to prove," Fultz wrote in his tweet. "To all the fans. keep riding with us. I'm going to approach this recovery with all my heart and be the best teammate I can be to this organization. Faithful to the grind."
Fultz signed a three-year, $50 million extension last month and was finally showing the promise that made him a No. 1 overall pick as he led the Magic to a quick start this season. He came in averaging a career-best 14.3 points along with 3.6 rebounds and 6.1 assists in seven games.
Fultz was drafted by the Philadelphia 76ers as part of their lengthy rebuild but struggled for years with a difficult-to-diagnose shoulder injury ultimately determined to be thoracic outlet syndrome, a nerve ailment that affected the feeling in his arm and hand. He was traded to the Magic in February 2019.
"It's a huge blow for us," said Magic center Nikola Vucevic, whose team also will be without standout forward Jonathan Isaac this season because of an ACL tear. "Unfortunately for [Fultz] this is really sad, because for two years he had the injury with his shoulder, then last year he finally got to play and this year it was supposed to be a big year for him. He was ready and he started the season out awesome. This really sucks for a guy like him who has worked his way back. It's hard to see, and you feel for the guy.''
Terrence Ross, who scored 20 points off the bench to lead the Magic, expressed confidence that Fultz would bounce back from his injury.
"If anybody can handle it, it's 'Kelle," Ross said. "He got the heart of a lion. He's super talented. He's always positive. I know he will be able to handle this, and we all got his back and will be here for him.
"You hate to see this, especially for a guy who had already fought through so much and came back and was balling. Now this. It is one of those things that will make him stronger, and he will come back from this. I have no doubt."
The Associated Press contributed to this report.