The 37-year-old, who has been coaching and training with the club's reserves, came on as a 59th-minute substitute shortly after his return to action for the rest of the season was made public and he was heavily involved as United held off a fightback by 10-man City.
United have suffered a succession of injury problems this season, with central midfielders Tom Cleverley, Darren Fletcher and Anderson ruled out for large chunks of the campaign.
Scholes was given a rapturous ovation by the United fans and his first touch was a neat exchange of passes with Michael Carrick.
He sprayed the ball around confidently to slot seamlessly back into the United midfield, even managing a crisp shot on goal which was easily saved.
"He has kept himself in great shape and I always felt that he had another season in him," manager Sir Alex Ferguson said in a statement. "It's terrific to have him back."
Scholes played 676 matches for United between 1994 and 2011, scoring 150 goals and helping them win two Champions Leagues, 10 Premier League titles and three FA Cups.
"I've been pretty clear since I stopped playing that I miss it," he said.
"I'm delighted the manager feels I can still make a contribution to the team and I'm looking forward to playing my part in trying to bring more success to this great club."
Scholes played 66 times for England before retiring from internationals in 2004 to extend his club career.
Carrick and Ryan Giggs have been the only fit and experienced central midfielders available to Ferguson in recent weeks.
Carrick has also been forced to play in defence and United have lost their last two Premier League matches, falling three points behind City at the top of the table.
His team-mates are delighted to have Scholes back, if a little surprised.
"It was a bit of a shock to be honest, we didn't know until we were in the dressing room, but he's a great player," said striker Wayne Rooney.
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.