Ramirez slid into second base, completing an RBI double that trimmed the White Sox lead to 5-1 at Progressive Field. As Ramirez touched the bag, hands first, he slid through the legs of Anderson in front of second-base umpire Malachi Moore.
Anderson looked down at Ramirez, who held out a hand as if to see if his opponent might help him up. Anderson did not, and when both gained their balance on their feet, they squared up to fight.
Punches were exchanged as teammates and coaches arrived on the scene, and Ramirez knocked Anderson to the ground with a right hand.
"He said he wanted to fight and I had to defend myself," Ramirez said after the game, a 7-4 loss for Cleveland.
Both managers -- Cleveland's Terry Francona and Chicago's Pedro Grifol -- were also ejected, as was Guardians third-base coach Mike Sarbaugh and relief pitcher Emmanuel Clase.
"It's not funny, but boys will be boys," Francona said after the loss.
Francona told reporters he wasn't exactly sure what prompted the fight, but said that before the brawl, Anderson had been told by one of the umpires to stop jawing at Guardians rookie Gabriel Arias.
Ramirez and Anderson likely face suspensions, and perhaps other participants do as well. The teams play their series finale Sunday afternoon, though Anderson was not in the lineup for the White Sox in what Grifol said was a planned off-day.
Ramirez said he felt Anderson was being disrespectful. On Friday night, Anderson pushed Guardians rookie Brayan Rocchio off the bag at second following a slide, leading to a call that was controversially reversed by the umpires.
Grifol didn't want to comment directly about the ugly incident.
"There are a lot of people upset," he said. "Thank God I haven't heard of any news out of the trainer's room. I'm not going to talk about it. I'm going to let MLB figure this out. They've got some work to do."
Anderson, who was led to the dugout by his teammates and forced down the steps, eventually returned to the scrum, before being surrounded by teammates again. He did not speak with reporters after the game.
"We love Timmy," White Sox shortstop Elvis Andrus said. "We're always going to support him and have his back. He plays with passion and gives 100 percent on the field. Stuff like this happens."
The Associated Press contributed to this report.