With a following of over 11,000 at Old Trafford, it was the biggest day in the history of the part-timers, who far from disgraced themselves.
But after being held at the Pirelli Stadium a week last Sunday, United made no mistake second time around.
And with the exception of midfield player Richie Jones, who has since joined Royal Antwerp on loan, it was the same side that played in the first game.
It was still essentially a reserve side as Sir Alex Ferguson made eight changes from the starting line-up in Saturday's derby, with only John O'Shea, Darren Fletcher and Mikael Silvestre remaining.
But with Gary Neville, Rio Ferdinand, Ruud van Nistelrooy, Ryan Giggs and Edwin Van der Sar on the bench there was plenty of experience to fall back upon had things not gone to plan.
But it took the Red Devils less than seven minutes to break the deadlock when Louis Saha scored his sixth goal in only six starts this season.
Kieran Richardson broke down the left and his low cross was slotted home from six yards by Saha.
United scored their second goal midway through the half to more or less guarantee their fourth round place and a trip to Wolves.
Ole Gunnar Solskjaer broke down the right and his low cross eluded the Brewers defence, finding Silvestre on the far side and he whipped in the ball for Giuseppe Rossi to score with a glancing header from close range.
United should half scored a third goal on the stroke of half-time when Saha burst through on to Rossi's flick, but he miscontolled in front of goal as the opening went begging.
Richardson scored a fantastic solo goal to make it 3-0 early in the second half. The left-winger raced on to Rossi's flick and, from his own half, he outpaced the visiting defence to score with a terrific shot from just outside the penalty area.
Substitute Ryan Giggs added a fourth goal midway through the second half with an angled shot from the right side of the penalty area after playing a delightful return pass from Rossi.
And the scoring was completed in stoppage time when Rossi scored his second and United's fifth with a glorious shot from the edge of the area following Giggs' corner.