Williams was scheduled to start Monday against San Diego, but he had an appendectomy Sunday. Kohl Stewart was recalled from Triple-A Iowa to take Williams' turn against the Padres.
And Chicago's offense made Stewart feel right at home. Javier Báez and Patrick Wisdom each homered twice, helping Stewart and the Cubs to a 7-2 victory over San Diego.
Despite a rash of injuries, the Cubs won 12 of 16 heading into the series with San Diego. Williams, Jason Heyward, Jake Marisnick, Nico Hoerner, Matt Duffy, Alec Mills and Justin Steele have gone on the IL since May 10.
"You want to cry uncle sometimes," manager David Ross said with a chuckle. "But it is what we're dealing with and guys have done a nice job of coming up and helping us win ballgames."
There is no timetable for Williams' return. Ross said the pitcher has a follow-up appointment on Thursday.
While Williams went on the IL, a move that was made retroactive to Friday, it looked as if a couple of key players for Chicago were moving closer to playing again.
First baseman Anthony Rizzo was out of the starting lineup for the sixth consecutive game because of back tightness. But Rizzo took some swings and fielded grounders before the matchup with the Padres.
Heyward (left hamstring strain) and Marisnick (right hamstring strain) also worked out on the field.
"We're on the verge of getting some guys healthy, which is the good news on the back end of some bad news," Ross said.
The Associated Press contributed to this report.