Punches were thrown from both sides as his new team lost 124-115 to the Houston Rockets at Staples Center.
Rockets guard Chris Paul alleges that the Lakers' Rajon Rondo spat in his face, which then led to a fracas.
James, a four-time NBA Most Valuable Player, acted as peacekeeper as Rondo, Paul and Brandon Ingram were all ejected for their part in the brawl.
Ingram committed a foul on the Rockets' James Harden, before Rondo allegedly spat in Paul's face, with punches then thrown.
The altercation occurred with four minutes 13 seconds remaining, when the Lakers were trailing by one point.
The home side lost two players, Rondo and Ingram, while the Rockets had Paul removed from the court.
After the game, Rockets forward Carmelo Anthony said of the alleged spitting incident: "I was right there. I was standing right next to Chris.
"That is unacceptable. You don't do that. You don't do that, to nobody. In sports, on the streets, that's blatant disrespectful right there."
James, who has lost his two NBA games since moving to the Lakers, declined to comment on the incident.