It had been anticipated Sir Alex Ferguson would only tinker with his starting line-up from the Bernabeu three weeks ago.
Instead there were four changes, with Ryan Giggs handed his 1,000th senior game, and Nani, Tom Cleverley and skipper Nemanja Vidic also included.
It meant no place for Jonny Evans, injured Phil Jones and Saturday's hat-trick hero Shinji Kagawa.
However, the absence of Rooney was the biggest bombshell after his return to first-team duties against Norwich at the weekend following a sinus infection.
Rooney was named on the bench, where he was joined by Javier Hernandez, Kagawa, Ashley Young and Antonio Valencia.
As anticipated, Cristiano Ronaldo was making his first appearance at Old Trafford since his world record £80million exit for Madrid in 2009.
Coach Jose Mourinho did make a change, though, with Gonzalo Higuain replacing Karim Benzema in a match in which they had to score in order to avoid exiting on away goals.
- Sports & Recreation
- Ryan Giggs
- Sir Alex Ferguson
- Tom Cleverley
- Nemanja Vidic
- Shinji Kagawa
- Jonny Evans