The team placed Wells on the NFL's new injured reserve/designated for return list. That allows him to return to practice Nov. 7 and to play in the Cardinals' home game against the St. Louis Rams on Nov. 25.
Quarterback Kevin Kolb called it "a huge loss."
"He's a big part of our team and he's a nice counter to the rest of our backs, the way he runs," Kolb said, "and a leader. He's stepped up as a big leader the last year and a half."
The injury will leave the bulk of the running game load on second-year pro Ryan Williams, who had been splitting time with Wells. Williams rushed for 83 yards on 13 carries against Philadelphia.
Williams said the performance helped him get over his critical fumble the previous week at New England, which gave the Patriots a chance at the game-winning field goal, an attempt that missed. He said he expects five or 10 more carries against Miami on Sunday and feels no added pressure.
"When times like this, when your number is called, you're supposed to step up to the plate," Williams said. "... There's no pressure, man, this is something I've wanted to do for the longest and that's play a lot of football. I'm getting the opportunity so I have to do something with it."
Kolb said the team is confident in Williams' ability to step into a larger role.
"We all know that he can, that he has the ability to," Kolb said. "I thought he had a nice ending to the game last week to build his confidence. He's working hard, even today, to make sure that he's up to date on everything, he's sharp with everything mentally."
In a corresponding move, the Cardinals re-signed running back Alfonso Smith, a backup for Arizona last season who was released in the team's final roster cuts on Aug. 31. The other running backs on the Arizona roster are LaRod Stephens-Howling and William Powell.
Stephens-Howling, however, is used primarily in specific situations that maximize his quickness and minimize the impact of his 5-foot-7 height. He missed Wednesday's practice with a hip flexor.
Powell, who won a spot on the roster with his play in the preseason, was inactive the first three games.
While Wells will be eligible to play the final six games of the season, there's no guarantee he will be healthy enough to do that.
"With the type of injury he has, we anticipate six to eight weeks at least before he'll be ready to go," Whisenhunt said after Wednesday's practice. "So if you look at where we still have games left, it will be good to have him back at that point."
Wells was Arizona's first-round draft pick, the 31st selection overall, out of Ohio State in 2009. He is coming off his best season, when he rushed for 1,047 yards despite a sore knee that bothered him most of the season and kept him out of the finale against Seattle. He rushed for a franchise-record 225 yards at St. Louis last Nov. 27.
This season, he was off to a slow start, gaining just 76 yards on 29 carries, an average of 2.6 yards per attempt.
At 6-foot-2 and 229 pounds, Wells' power running style complemented the more shifty approach of the 5-9, 207-pound Williams. Powell is just 5-9 and 207 pounds, probably a reason the team re-signed the 6-1, 207-pound Smith, who played in 15 games last season, rushing for 102 yards on 30 carries and a touchdown. He also caught three passes for 21 yards and had five special teams tackles.