The margin of victory is harsh on the Blades who, for periods, put the Premiership side on the back foot, with Jamie Murphy going close on a couple of occasions.
Chris Porter and Neill Collins returned from injury for Danny Wilson, who will take a number of positives from the encounter at the Madejski Stadium.
Porter returned to United's starting line up for the tie, replacing Flynn, who dropped to the bench and was joined by the fit-again Collins. Reading were captained by ex Blade Leigertwood. The return of Porter saw him partnered with ex Royal Kitson in attack, with Murphy and Blackman the support from the flanks.
There was little to report before the third minute when everyone inside the Madejski - including Messrs McDermott and Wilson - rose to their feet and applauded in appreciation of the efforts of former Blades and Reading defender Chris Armstrong, who had to retire from the game early. The committed full-back wore the number 3 shirt at both clubs.
However, it was just the home fans cheering on six minutes when Reading took the lead. Robson-Kanu delivered a cross from the left and HUNT outjumped Westlake to head across Long and into the net.
McMahon curled a free-kick over in response and the Blades went close to levelling on 18 minutes. McDonald's ball to Blackman wide on the right was perfect and the latter danced around his marker and passed across goal where Maguire got a slight touch but the ball rolled just wide of the post.
After Reading's opener, United saw a lot of the ball. Blackman was prominent, McDonald tried his luck from distance on a couple of occasions, whilst another McMahon free-kick was deflected wide. On 33 minutes, the visitors created another good chance, on this occasion Murphy was prominent and swung in a cross for Porter to head just wide.
United's attempts to level continued. Porter flicked on for Kitson to find Murphy, whose shot was straight at Federici, and then Blackman almost got on the end of a searching McDonald pass.
However, the good work was ruined on 40 minutes when Reading added a second. Long pushed away a Le Fondre shot but the young goalkeeper could do little when LEIGERTWOOD stepped inside Doyle and fired into the top corner from 20 yards.
The Blades trudged off at the break but their endeavours did not deserve a two-goal disadvantage and at the start of the second period it was visitors who were quickly on the offensive, challenging from a Blackman corner and crosses from Higginbotham and Murphy.
But fortune was with the home side, that was obvious with the third goal on 50 minutes. After escaping Maguire, HUNT connected with McCleary's cross with a scuffed effort that got the better of Long. It became four soon after, this time McCLEARY was the finisher, turning inside Westlake on United's left before picking his spot in the opposite corner. Between the third and fourth goals, Kitson volleyed over for the Blades.
Flynn replaced Porter with Blackman moving to a central role, whilst just after the hour goalkeeper Federici had to push away a shot from McDonald. From the subsequent corner, Maguire and Doyle were involved in a melee before Kitson laid off to Murphy, who saw his shot beat Federici but Kelly kicked off the line.
The Blades went close to pulling a goal back when Flynn was free to meet a Blackman cross but the header was just wide. It would have been a consolation and the least the visitors deserved but home side took their place in the fifth round draw after an uneventful closing spell.