The former Scotland captain came through the youth ranks at United before making over 300 first-team appearances and helping the club win a host of honours, including five Premier League titles, the FA Cup and Champions League.
He moved to West Brom in 2015, temporarily ending a 20-year association at United, and finished his playing career at Stoke but returned to Old Trafford last October to take up a coaching role with the under-16s at the club.
The 36-year-old will now step up to help with first-team duties on a full-time basis.
United manager Ole Gunner Solskjaer said on the club's website: "Darren has the United DNA running through his veins and he knows exactly what it takes to be a Manchester United player.
"He is at the start of his coaching career and his experience both on and off the pitch along with his winning mentality, commitment and hard work will be a great addition to the staff."
Fletcher, who was capped 80 times by Scotland, added: "I am delighted to be returning to the club as a first -team coach.
"It's a very exciting time for this young team and I am looking forward to taking the next steps in my coaching career by working with Ole and his staff."
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