The news had been widely expected following the exits of Mike Phelan and Eric Steele since David Moyes' appointment as Sir Alex Ferguson's successor.
It has been claimed in Holland that Meulensteen is considering an offer to link up with Guus Hiddink at super-rich Russian outfit Anzhi Makhachkala.
"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," said the Dutchman.
"I wish everyone at this great football club all the best."
Executive vice-chairman Ed Woodward added: "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 he has given great assistance to Alex and Mike 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."
With three of the most senior members of Ferguson's back-room team now gone, it is anticipated Moyes will bring in some new faces next week.