Harden, taken third overall by Oklahoma City in the 2009 NBA Draft, won the Sixth Man Award after averaging a career-high 16.9 points per game in the 2011-12 season as his team compiled the league's third-best record.
The Thunder guard, who was recently was added to the pool of finalists for the U.S. Olympic team for the London Games, came off the bench in 60 of 62 games he appeared in.
He received 584 of a possible 595 points, including 115 of 119 first-place votes, from a panel of U.S. and Canadian sportswriters and broadcasters, the NBA said in a statement.
To be eligible for the award, a player must come off the bench as a reserve in more games than he starts.
Louis Williams, who led the Philadelphia 76ers in scoring despite not starting a single game, finished second in voting while Jason Terry of the Dallas Mavericks, who won the award in 2009, was third.