The Red Devils had six different scorers on the day as the win helped ease the pressure on manager Ole Gunnar Solskjaer.
Tranmere got the better of Premier League opposition Watford in the previous round but this was a difficult hurdle to navigate against one of the FA Cup’s most successful sides.
United got the opening goal of the game through an unlikely source as captain Harry Maguire surged forward from the back and unleashed a thunderbolt from 20 yards for his first goal for the club in the 10th minute.
Diogo Dalot, playing as a right wing-back, got his name on the scoresheet when he linked up well with Anthony Martial before cutting inside the Tranmere defence and firing into the far corner in the 13th minute.
The hosts failed to learn their lessons as they allowed Maguire another foray from the back before slipping it to Jesse Lingard, who picked his spot and curled the ball into the right corner in the 16th minute.
Phil Jones also got in on the act when his looping header from Andreas Perreira’s corner zoomed over a defender on the line into the net in the 41st minute.
If the identities of United’s first four goal scorers were surprising, the next two were more predictable as Martial cut onto his right foot and curled in a fifth on the cusp of halftime.
Ten minutes after the break, Solskjaer’s men were awarded a penalty after substitute Tahith Chong was brought down by Tranmere goalkeeper Scott Davies, allowing Mason Greenwood to step up and send the goalkeeper the wrong way for the visitors’ sixth.
