With eleven changes from the side that lost to Liverpool on Sunday, the Red Devils managed to ease past the Championship side to send themselves through to the quarter-finals.
Promising teenage striker Danny Welbeck again showed his love for the cups competition, netting in the 6th minute to give the visitors the dream start.
The 18-year old was gifted a free header from an Anderson corner and finished with precision to again prove his worth to Ferguson.
The second goal came from a man at the other end of his career just prior to the hour-mark.
Michael Owen, who was given a start by Ferguson, managed to work his way past two Barnsley defenders before clipping the ball past keeper Luke Steele to make it 2-0 and in the end it was enough for United to advance.
But there was a slight worry for manager Sir Alex Ferguson as he saw his team finish with ten men for the second time this week when Gary Neville was given his marching orders in the 63rd minute for making contact with Adam Hammill, following the red card defender Nemanja Vidic received in the loss to Liverpool.
Despite that, the Red Devils move through to the quarters and are a step closer to defending their crown.