The MLS side had gone ahead in the first half through Gibbs, but substitute Rooney chipped his side level before Rafael and Nani slotted home for the win
Nani and Rafael grabbed the other goals as the Premier League champions turned around a first-half deficit.
Ferguson sent out a relatively strong side with a handful of first-teamers including Patrice Evra, David De Gea and Michael Carrick. New signings Phil Jones and Chris Smalling rekindled their England Under-21 partnership in the centre of defence.
Dimitar Berbatov was given a chance to impress alongside youngsters Mame Biram Diouf and Danny Welbeck in attack.
But it was the MLS side who make the first breakthrough after 13 minutes as Cory Gibbs out-jumped Jones and nodded past De Gea.
The Premier League champions responded quickly as Welbeck flashed a shot wide and was nearly played in by Gabriel Obertan a few minutes later - the Frenchman impressing in midfield in the opening period. Obertan then produced a moment of magic, flicking the ball over the defender, but firing wide.
The home side grew in confidence as the first half petered out and Patrick Nyarko had a shot well saved by De Gea.
As expected Ferguson rung the changes during the break and those switches continued into the second half with Federico Macheda, Wayne Rooney, Anderson, Ryan Giggs, Nani, Rio Ferdinand and Jonny Evans among those introduced.
The second half begun with Smalling finding the net, only to have his effort ruled out for offside.
The former Fulham man was then on the back foot, and lost out to Nyarko who squared to Husidic but the Chichago forward made an utter mess of the chance to put his side 2-0 up.
Rooney and Macheda both drilled in efforts in an attempt to get United back into it, but failed to test Sean Johnson in the home side's goal.
But the pressure soon paid off as Rooney calmly chipped Johnson to draw his side level with 20 minutes left.
Six minutes later team-mate Rafael made it 2-1 to the visitors; slotting in from a tight angle.
Chicago made a flurry of late substitutions to try and swing the game back in their favour but found themselves two goals down when Nani finished smartly.
United played out the rest of the game with relative ease as the gulf in class began to show, but the MLS side will be buoyed by their efforts against the Premier League champions.
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