The 24-year-old suffered a lateral meniscus tear during the second quarter of Oklahoma's 105-102 victory over the Houston Rockets on Wednesday, a win that put them up 2-0 in the first-round best-of-seven play-off series.
Westbrook, a three-time NBA All-Star who averaged 23.2 points during the regular season, will have surgery in the coming days but no timetable has been set for his return, the team said in a statement.
"Our players' health is our first and foremost concern," Thunder General Manager Sam Presti said. "The Thunder's medical team and several specialists we consulted with determined that Russell undergo a procedure to address the issue.
"We have thoroughly discussed this with Russell. Despite being the competitor and team mate that he is, he respects and understands the decision and is committed to come back even stronger.
"Certainly Russell is a leader and core player for this team, but we are in the midst of the play-offs and I know other players are determined to step up and contribute."
Westbrook, who has never missed an NBA game during five seasons in the league, was injured while going for a steal when his knee collided with Rockets rookie Patrick Beverley's hip.
Oklahoma City forward Kevin Durant, a four-time All-Star, said the team would have to "rally around each other and play Thunder basketball" in Westbrook's absence.
"We're not trying to rush him or bring him back ahead of schedule," Durant, 24, said. "We want to make sure he's healthy and his knee is right.
"That's our only concern with it right now. All he has to worry about is him getting healthy."
The top-seeded Thunder, who won the Western Conference last season, are widely regarded as the biggest challengers to the NBA champion Miami Heat during this campaign.
Oklahoma City will next be in action on Saturday when they visit the eighth-seeded Rockets in Houston for Game Three.
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