Sizemore initially hurt his left knee during spring training but the 27-year-old played through the pain before aggravating the injury on May 16 against the Baltimore Orioles.
Three days later, he was put on the disabled list. Following consultations with several doctors, he is scheduled to have arthroscopy surgery in Vail, Colorado with Dr. Richard Steadman, a pioneer of microfracture surgery.
"It's a big blow," Indians manager Manny Acta told the team's official website (http://cleveland.indians.mlb.com). "He's still an important part of this ballclub, even when he's struggling offensively.
"He brings so much to the table. His speed never goes into a slump, he's a great defender and the presence he brings to our ballclub is not easy to replace."
Three-time All-Star Sizemore was batting .211 this season with no home runs and 13 RBIs in the number two spot for the Indians when he went on the disabled list.
Cleveland (18-29) prop up the American League's Central standings, having lost seven of their last 10 games.
(Writing by Mark Lamport-Stokes in Los Angeles; editing by Pritha Sarkar)