If that wasn't bad enough, leading scorer Joe Johnson rolled his right ankle in the third quarter and did not return.
X-rays were negative, but Johnson wore a walking boot as he and his teammates went to their bus before heading home for Game 3 on Saturday.
"I can't see me not playing," Johnson said. "I don't want to let this opportunity go by. We're down 0-2. I want to be out there for my teammates. Hopefully in 48 hours it will feel a lot better."
Horford was out with a sprained right ankle, while Williams has a sprained right wrist. Both missed games in Atlanta's opening round series against Miami. Coach Mike Woodson said both were reinjured in Cleveland's Game 1 win in the opener Monday night.
In the regular season, Horford averaged 11.5 points and 9.3 rebounds, while Williams averaged 13.9 points and 6.3 rebounds.
"We've had this problem through the course of the season," Woodson said of the injuries. "There's no excuse. The guys who are dressed have to step up and play."
The Associated Press contributed to this report.