Isaac stayed on the ground for an extended period before being stretchered off the floor with what the team announced is a hyperextended left knee.
After receiving an MRI on Thursday, Orlando ruled him out for at least eight-to-10 weeks.
The injury occurred after Isaac stripped Bradley Beal, accelerated down the floor and rose for a layup. He tangled with Beal, who was backtracking to contest the shot, and crumpled to the court.
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Isaac, 22, has been a defensive monster this season. He averages 1.6 steals per game and 2.5 blocks per game. He is considered the most promising piece of a Magic team trying to break a perpetual cycle of mediocrity since the departure of Dwight Howard almost a decade ago.
Orlando is no stranger to serious lower-body injuries in recent years — fellow wing Aaron Gordon has dealt with knee problems throughout his career and is now sidelined with an Achilles injury.
The Magic (14-19) recently got center Nikola Vucevic back from a foot injury.
