The injury is a blow to an already depleted defense that had to play two backup linebackers Sunday during a loss to the Ravens.
Brown said he injured his knee in the third quarter of a game against the Saints on Nov. 11. He was in a knee brace the following week and did not practice, but said he couldn't discuss what specifically was wrong.
"Coach says I can't speak about injuries," Brown said last Wednesday. "It happened in like the third quarter but I kept playing. So I'm not really sure."
Brown signed with the Bengals in the spring after spending the first four years of his career in Buffalo. He never missed a game with the Bills and was tied for the NFL lead in tackles last year.
He has only played in seven of Cincinnati's 10 games this season. He injured his ankle in the season opener, which caused him to miss the next two games. He also tweaked the ankle against the Dolphins on Oct. 7 but played the next four games.
His knee injury will end his season, and his likely replacement is Hardy Nickerson, who has filled in for Brown.