Westbrook will miss at least 27 games.
"He will be missed," coach Scott Brooks said before Oklahoma City's game Friday night against the Charlotte Bobcats. "Obviously we are a very good team with him, and without him we're still going to be a very good team."
General manager Sam Presti said in a news release earlier in the day that Westbrook has been playing pain-free, but "recently had experienced increased swelling" in his right knee.
"After consultation and consideration by his surgeon in Los Angeles, a plan was established to monitor the swelling that included a series of scheduled MRIs," Presti said in the release. "On the most recent MRI it was determined by the surgeon that there was an area of concern that had not previously existed, nor was detectable in the previous procedures, and it was necessary to evaluate Russell further. The consulting physician determined that arthroscopic surgery was necessary to address the swelling that was taking place."
Brooks said Reggie Jackson, who is averaging 12.5 points, will start. Jeremy Lamb will also see increased playing time in Westbrook's absence.
"Guys believe in what he does for our team," Brooks said of Jackson. "He's only going to get better. He's a young point guard in this league.
Westbrook's knee problems began in April when he tore his meniscus in the second game of the Western Conference playoffs, sidelining him for the remainder of the postseason and all but ending Oklahoma City's chances of reaching the NBA Finals.
He had a second arthroscopic surgery as the Thunder were preparing for training camp after developing inflammation in the knee. However, Westbrook missed only two regular-season games before returning to the floor.
Oklahoma City has since gone on a 21-3 tear with Westbrook in the starting lineup.
The five-year NBA player is averaging 21.3 points, seven assists and six rebounds for the Thunder, who entered Friday night's game with a 23-5 record, a half-game behind the first-place Portland Trail Blazers in the Northwest Division.
Oklahoma City has won 10 of its last 11 games.
In his last game on Christmas, Westbrook didn't look like a player who was in pain, finishing with 14 points, 13 rebounds and 10 assists in a 123-94 rout of the New York Knicks.
Brooks said he didn't know the knee was an issue until after Wednesday's game.
"He's passed every medical benchmark and he was playing great basketball, probably some of the best basketball in the entire league," Brooks said. "We're looking forward to him coming back and getting back to the level that he has played at—and he will."