Harrison is expected to miss Monday night's game against the San Francisco 49ers, though he has appealed the suspension, his agent, Bill Parise, told The Associated Press.
Harrison's appeal is scheduled for 2 p.m. ET Wednesday via phone. The appeal will be heard by Ted Cottrell, jointly appointed by the NFL and the players' association to hear such cases.
Harrison becomes the first player to be suspended for a helmet-to-helmet hit at a time when the NFL commissioner Roger Goodell has attempted to enforce enhanced player safety rules.
While he is suspended, Harrison cannot practice with the Steelers or be at the team's facility or a stadium where they will be playing. He is scheduled to be reinstated Dec. 20.
Harrison had restructured his contract in August, taking his base salary down to $1.25 million. If he misses one game, he will forfeit $73,529.
Steelers coach Mike Tomlin said the team respects the league's decision
while acknowledging Harrison's play was a foul.
"We're disappointed for James because we know how hard he's
worked to play within the rules," Tomlin said. "We accept the
judgment rendered by the league office and we'll move forward."
Harrison's hit on McCoy was his fifth illegal hit against a quarterback in the past three seasons. In addition to the fines he has received for hits on quarterbacks, he also has been fined twice more for unnecessary roughness for other hits during that time period.
Harrison posted a thank-you message to his fans on his Twitter page after the suspension was announced.
"Thank you to all my fans and supporters, I'm just going to move on from here and get ready for my next game," he tweeted.
The 33-year-old Harrison has eight sacks this season despite missing a month with a fractured right orbital bone and dealing with persistent back issues.
He's been quiet this season following a turbulent spring in which he took shots at Goodell, calling the commissioner a "crook" and a "devil."
Harrison later apologized, saying his comments were "inappropriate," though both he and his teammates have been critical of the league's crackdown on what it considers dangerous and overly aggressive play.
On Monday, Harrison remained adamant that he did nothing wrong.
"I don't think a suspension is worthy," Harrison said. "I don't think it's worthy of anything, but that's just my own personal thoughts."
Harrison slammed into McCoy just as the quarterback released the ball, with the helmets of the two players colliding before McCoy tumbled to the ground. He laid on the Heinz Field turf for several moments before slowly making his way to the sideline, though he returned a few plays later to throw a game-deciding interception in the end zone.
McCoy suffered a concussion on the hit.
Harrison received a penalty for roughing the passer on the play and said Monday that should be enough. The All-Pro believes the instant McCoy tucked the ball he became a runner and therefore fair game.
"Well, he took off running with it, and at the last second he, like, chucked and ducked," Harrison said. "So, people can see it."
The hits led the NFL to take aggressive steps to better protect defenseless players. The new rules frustrated Harrison and also dented his wallet. He was fined $125,000 alone in 2010 for taking what were considered illegal or unnecessary shots.
Though there has been an emphasis to play by the rules, the Steelers have been fined at least 13 times for illegal hits this season. Safety Ryan Clark was fined $40,000 after being flagged for helmet-to-helmet hits in successive weeks.
The Steelers were the only team in the league to vote against the new collective bargaining agreement in August, citing the lack of a proper appeals process regarding fines and suspensions as one of their main concerns.
Tomlin refused to take issue with the fines or the penalties and doesn't believe it will affect the way the NFL's second-ranked defense plays the game.
"I'm not ready to paint with that kind of brush at this juncture," he said. "We've got a job to do."
Information from ESPN NFL Insider Adam Schefter and The Associated Press was used in this report.