Orioles vice president Dan Duquette confirmed the 22-year-old US star would miss the remainder of the campaign and be unavailable should Baltimore advance to the October playoffs.
Machado was batting .278 with 12 home runs and 32 runs batted in over 82 games for Baltimore this season.
Machado sprained a right knee ligament when he fell awkwardly while batting against the New York Yankees on August 11.
Last season, Machado missed the final week of the regular season after tearing a left knee ligament and did not take the field for the Orioles this season until May 1.
Neal ElAttrache, the Los Angeles Dodgers orthopedic surgeon who repaired Machado's left knee last year, will also operate on his right knee in the next few days, Duquette said.
At 73-53, the Orioles lead the American League East division by eight games over the Yankees.