Patient approach work between Cleverley and Valencia culminated in Nani controlling with his left and firing a 15-yard right-footed effort into Federici's far corner. Joy and relief mingled as Old Trafford roared its delight.
That bellow had barely subsided when Reading almost silenced all-but the small pocket of travelling supporters, as Adam Le Fondre hooked in a shot which required a fine reaction stop from De Gea. It proved a pivotal moment in the game, as United struck decisively just seconds later.
Again Nani was involved, speeding down the right flank and curling in a magnificent cross which Chicharito reached ahead of Federici to nod into the untended goal. Just as it seemed that United's progress thereafter would be a smooth process, however, Reading demonstrated the pluck which has punctuated their season to date.
Hunt's troublesome presence prompted the ball to bobble off Smalling, and McAnuff pounced, holding off the attempted challenge of Alexander Buttner and steering a finish past the exposed De Gea.
Michael Carrick was introduced to bring calm and perspective to United's play, and his steadying influence was apparent as the dying stages, including four added minutes, were navigated comfortably.
United might have added a third as Chicharito's stinging effort was fended away by Federici and Nani volleyed the rebound just wide, but there was one major fright to survive as Shorey curled in a fine free-kick which pinballed around rhe six-yard box before deflecting behind.
Federici was required to keep out another Chicharito piledriver and Nani dipped a 30-yard free-kick narrowly over the bar, but the scoreline remained sufficient to prolong United's interest in all three major competitions.