Williams crashed hard into the boards during the second period.
The 29-year-old right winger was on the ice for several minutes before being helped to the dressing room.
Williams was off to a relatively slow start with two goals and seven points through 14 games, but was still fifth on the team in scoring. He will now likely miss at least two months.
"Losing Willy was a blow to us," Detroit coach Mike Babcock said. "He's playing more minutes and in more situations than we anticipated. But that's just the way it's gone."
The Red Wings were already without winger Johan Franzen, the team's No. 2 scorer last season with 34 goals, who tore the anterior cruciate ligament in his left knee during the third game of the season and is out until February.
Detroit is also missing fourth-year center Valtteri Filppula, who broke his wrist at the end of October and will be out until late December.
"There's no sense worrying about the guys who aren't available," Babcock said. "We've got to find a way as a group to get a win."
"We're not going to be able to score as we did," Babcock said. "We're going to have to do a better job defensively, and we're going to have to get good goaltending and good specialty teams."