The Dutchman, who initially joined the club as a youth coach in 2001, was promoted to first-team coach upon his return to Old Trafford in 2007.
United's executive vice-chairman Ed Woodward told the club's official website: "I'd like to thank Rene for his contribution to the club, particularly since he returned to Old Trafford in 2007.
"He has been first-team coach for five years and in that time has given great assistance to Sir Alex Ferguson and Mick Phelan in keeping the team at the top of the game not only in this country but in Europe as well. On behalf of everyone at United, I wish him well for the future."
Meulensteen added: "I would like to thank Sir Alex Ferguson, the owners, all colleagues, players and fans who made my time at Manchester United very special and one I will never forget. I wish everyone at this great football club all the best."
Meulensteen is reportedly keen to remain in England.