The Bryans, who never faced a break point, broke Knowles twice in the opening set — in the fourth and eighth games. In the second set, Bhupathi was broken twice, also in the fourth and eighth games.
Bhupathi and Knowles, who are number two in the ATP Doubles Race, came into their third ATP final of the season having won 14 of their last 15 matches.
They won back-to-back titles in Memphis and Dubai without dropping a set before their 10-match winning streak ended in the quarter-finals at Indian Wells to eventual champions Jonathan Erlich and Andy Ram.
Knowles was attempting to become the 20th player in the Open era to win 50 career doubles titles while Bhupathi was aiming for his 44th career title.