Coach Dennis Allen announced the suspension but has not said publicly what McClain did to warrant the punishment other than calling it a team-related issue.
McClain was present at the start of practice Wednesday before being asked to leave amid speculation he might be released. Allen asked McClain to stay home from the facility on Thursday, saying there needed to be "consequences to his actions."
He told McClain on Friday that those consequences were a suspension, starting with Sunday's game against Cleveland.
"I'm not going to get into any of the specifics of anything that happened, that went into the decision," Allen said. "That's team-related matters. We're going to keep that within the family."
A source told ESPN that the Raiders were set to release McClain on Thursday.
Allen said he discussed the decision with general manager Reggie McKenzie but made the move himself. McKenzie said there was more than one incident that led to the suspension and it was possible that McClain had played his final game as a Raider.
"It's going to be on him. I don't feel the need to approach him. So far, he is not apologetic," McKenzie said. "We wouldn't suspend him unless it was something major, including all that stuff off the field and on the field and all that. I think a two-game suspension pretty much says it's an issue."
McClain is eligible to return from the reserve/suspended by club list on Dec. 10. The Raiders can add a player to the 53-man roster until then. McClain will lose about $114,000 of his $970,000 base salary.
Defensive tackle Tommy Kelly said McClain was very upset after being kicked out of practice on Wednesday. Kelly said he hopes McClain's career is not hurt by a "small disagreement" with a coach.
"Me personally, if I was him, I'd come back and do what they ask me to do and whatever happens after that, just deal with it," Kelly said. "But you never want to put yourself in a position where a team is going bad and they can just put all that on you. I just don't want him to get in a situation where he's the scapegoat. ... He's not what's wrong with the team. It's a collective effort. We all had our hands in it to this point so I just don't want him to be put in that position and know that if you do these certain things, that's how you're going to be cast."
McClain was the eighth overall pick in the 2010 draft after helping Alabama win a national championship the previous season. He has struggled so far in his career and has had his playing time sharply reduced in recent weeks.
In 41 career games with Oakland, McClain had 6½ sacks, one interception, one forced fumble, no fumble recoveries and did little to help improve Oakland's struggling run defense.
The Raiders (3-8) have allowed 169 points in losing the past four games and are on pace to give up the second-most points ever in a 16-game season.
After being essentially an every-down player for the first two years of his career, McClain was demoted after the first month of this season. He was replaced by rookie Miles Burris in nickel packages because of his struggles in pass coverage and because the coaching staff believed he tired too easily playing every down. He has gone from playing more than 90 percent of defensive snaps to just more than half the past seven games.
McClain also had problems off the field. He was involved in a shooting in Alabama last November when he left the team briefly during the season to attend a family funeral. McClain had been convicted of four misdemeanors in May but he appealed and the charges were recently dropped when the accuser told prosecutors he no longer wanted to pursue the case.
Recently acquired Omar Gaither will take McClain's spot in the lineup against Cleveland. Since being signed by Oakland on Nov. 14, Gaither has only played on special teams in two games but the coaches say he has learned the new system quickly.
Allen said third-string QB Terrelle Pryor will likely be active for the first time this season and could see some action. ... RBs Darren McFadden and Mike Goodson are listed as questionable after missing three games with sprained right ankles. They will both be game-time decisions. ... QB Carson Palmer practiced fully after being limited by a thumb injury Thursday and should be fine for the game Sunday.
Information from ESPN's Ed Werder and The Associated Press was used in this report.