Ohio State coach Jim Tressel made the announcement late Friday afternoon after the team went through a 40-minute walkthrough at the Los Angeles Coliseum.
"He's been getting treatment 15 times a day," Tressel told the assembled media just minutes after he told his team of the decision. "I guess if looks could kill he fought me. I just told the team because it's important our guys know what we thought we should do."
"He worked so hard, but my job is to keep his best interests at heart," Tressel told ESPN's Joe Schad.
The Trojans (1-0) will be playing their first game since an impressive 52-7 victory Aug. 30 at Virginia. Ohio State (2-0) has beaten in-state opposition Youngstown State 43-0 and Ohio University 26-14.
Wells, who rushed for 1,609 yards and 15 touchdowns last season, injured his right foot in the opener and without him, the Buckeyes had to rally to beat the lightly regarded Bobcats last weekend.
Tressel said early in the week that Wells would play, but it was a different story Thursday, when he said the 6-foot-1, 237-pound junior was doubtful because of lingering soreness in his foot.
Information from The Associated Press was used in this report.