United and City fans raised their commemorative scarves around the ground and stood in tribute to the 23 people, including eight of the famed 'Busby Babes', who died in the air crash 50 years ago last Wednesday।
But during the minute's silence, what appeared to be loud bangs were heard coming from outside the stadium.
Injured United captain Gary Neville, watching from the stands, appeared visibly shocked at the intrusion.
City supporters' groups had called for there to be a minutes' applause instead because they were worried some fans would not respect the wishes of their greatest rivals.
However, United insisted only silence was appropriate and both clubs urged all fans to cooperate, describing the disaster as a tragedy for Manchester.
Fears were heightened after a minute's silence at Wembley on Wednesday ahead of England's meeting with Switzerland was cut short after some spectators disrupted the tribute.
City boss Sven-Goran Eriksson said on Friday: "Football is one thing but when people die too early in an extremely bad accident, you have to respect that.
"It doesn't matter if you are wearing a blue shirt or a red shirt or whatever. It has nothing to do with football.
"We have to respect those who were doing the same job as we are doing today. It's sad and it should be respected. Don't be a fan for that minute."
Legendary City goalkeeper Frank Swift was among eight journalists who also perished when the plane carrying United home from a European Cup match in Belgrade crashed on take-off after refuelling in Munich.
Survivors of the tragedy were among the crowd for the Old Trafford derby, which is the culmination of a week of events marking the 50th anniversary.
Both clubs wore special plain kits for the match and United boss Sir Alex Ferguson and Eriksson placed wreaths in the centre spot ahead of the period of silence.
