Miller, a junior from Metuchen, N.J., suffered a torn meniscus in practice on Tuesday, and his post-surgery recovery is estimated at five months. Though the first six games of the season, he'd emerged as the No. 3 target for quarterback Landry Jones, with 10 of his 15 catches in 2010 coming in his last three games.
Senior Cameron Kenney is expected to fill Miller's role in the offense.
Miller made his first start of the season in Oklahoma's 52-0 shutout against Iowa State on Saturday night.
At 6-foot-4, Miller is the tallest member of the Sooners' receiving corps.
Unbeaten Oklahoma (No. 1 BCS, No. 3 AP) plays at fellow unbeaten Missouri (No. 11 BCS, No. 18 AP) on Saturday night.
David Ubben covers the Big 12 for ESPN.com. Information from The Associated Press was used in this report.