The superstar suffered the injury in the second quarter on a collision with Solomon Hill and did not return.
Atlanta (22-20) took advantage to remain the hottest team in the NBA with its eighth straight victory. John Collins led the way with 27 points and 16 rebounds at the Staples Center while the defense remained strong to force 16 turnovers.
It's the third time in four games the Hawks have held an opponent under 100 points.
Montrezl Harrell finished with 23 points as the Lakers (28-14) lost for the first time since the All-Star break.
John Collins, PF, ATL: 27 points, 16 rebounds, 3 blocks, 3 steals
Trae Young, PG, ATL: 14 points, 11 assists
Clint Capela, C, ATL: 8 points, 16 rebounds, 1 block
LeBron James, SF, LAL: 10 points, 4 assists
Montrezl Harrell, C, LAL: 23 points, 11 rebounds
Dennis Schroder, PG, LAL: 16 points, 7 rebounds, 4 assists, 2 steals
LeBron Leaves Game Early with Ankle Injury
It was a strong start for James, who distributed the ball well without forcing much himself.
The stats suddenly didn't matter after he suffered an injury in the second quarter while chasing a loose ball:
Though he initially stayed in the game, it was clear his ankle was bothering him, and he eventually headed to the locker room:
He was ruled out of the game before halftime.
LeBron still scored 10 points, reaching double figures as he has in every game this season, but the larger concern is his long-term health.
With Anthony Davis already out with an Achilles injury, it suddenly creates a major void for the Lakers.
Los Angeles was able to showcase its depth against the Hawks, quickly overcoming the injury to stay competitive.
The effort was still there in the second half as well, with Schroder especially working hard despite his own apparent ankle injury.
Harrell also had a solid performance off the bench with 23 and 11.
It still wasn't enough to keep up with Atlanta, which could be a concerning thought if James is forced to miss an extended period.
John Collins Displays Upside with Dominant Showing
Whether his future is in Atlanta or somewhere else, Collins showed he can be a difference-maker on the court.
The forward was a factor from the opening tip against the Lakers, playing physical inside to get buckets around the net:
He nearly had a double-double at halftime to keep the Hawks within one despite Trae Young being held to just four points in the first half.
Collins continued in the second half on his way to one of his best games of the season.
The 23-year-old is set to be a restricted free agent this offseason and "is drawing heavy interest ahead of the deadline," according to Zach Lowe of ESPN.
With his high level of play Saturday, Collins showed the Hawks should probably keep him around.
Young still made an impact in the game with 11 assists, but he didn't have his best game while shooting 6-of-18 from the field and 0-of-7 from three-point range.
Atlanta needed someone else to step up, and Collins was there for the big game.