The Nigerian forward saw action late in a match decided by an early Anthony Martial strike and a late Scott McTominay goal to go home celebrating after his first Manchester derby.
Odion Ighalo was introduced for Bruno Fernandes deep into the second half as the hosts condemned the champions to a 2-0 defeat at Old Trafford on Sunday.
The on-loan striker has netted three goals in his first six games since making a sensational deadline day switch to United, but Ole Gunnar Solskjaer decided to start with the attacking trio of Bruno Fernandes, Daniel James and Martial against the champions.
It was the Frenchman who handed the hosts a deserved 1-0 lead into half-time against City after half an hour. Fernandes chipped a free-kick into the path of Martial to volley past Ederson, who should have done a lot more to keep out the shot at his near post.
United should have doubled their advantage late in the half but had a strong penalty appeal rejected when Fred appeared to be caught by Otamendi.
The Reds defended doggedly in the second half as Guardiola's men cranked up the pressure to no avail.
Deep into injury time, substitute McTominay grabbed United's second goal to hand the visitors their first loss in six matches.
In a rush to get the ball forward, Ederson rolled the ball straight to McTominay around 40 yards from goal. The United youngster did not have to think twice, with his first time shot finding the net unguarded and leaving the City's keeper red-faced.
United have now gone ten games without defeat and are a mere three points behind Chelsea, who sit in the last Champions League qualifying spot.
