Rooney flicked home Carlos Tevez's left-wing cross 13 minutes from time to break the home side's impressive resistance.
Then, three minutes into stoppage time, Reading's frantic search for an equaliser backfired as Ronaldo broke clear to slot home the crucial second.
Defeat was hard on Reading, who had adopted an attacking approach to the game having not won any of their previous six in all competitions.
Reading boss Steve Coppell solved a defensive selection headache by playing midfielder Kalifa Cisse at centre-back, rather than hand teenager Alex Pearce a league debut against the champions.
Yet Coppell did plan on attacking, with striker Kevin Doyle moved to a wide midfield role and free-scoring winger Stephen Hunt moved into a central midfield role.
Owen Hargreaves saw an early United free-kick superbly tipped away by Marcus Hahnemann, but Reading's spirited and determined approach saw them carve out plenty of chances too.
Only a superb tackle by Nemanja Vidic denied Dave Kitson a clear strike a goal after Edwin Van der Sar had blocked at Leroy Lita's feet and Kitson was desperately unlucky not to open the scoring in spectacular style after half an hour.
Van der Sar raced from his goal and fluffed his clearance and Kitson's hooked left-foot shot from 45 yards out was headed for the empty net before Rio Ferdinand got back and stretched to head clear and save his keeper's blushes.
Sir Alex Ferguson reacted to his side's stuttering performance by bringing on Ryan Giggs at half-time and the Welsh winger's corner caused panic in the opening minutes of the half as Hahnemann punched the ball against Kitson and was relieved to see Cisse acrobatically clear off the line to prevent an embarrassing own goal.
Kitson and Hahnemann nearly combined at the right end for Reading when the keeper's long clearance bounced beyond Ferdinand and saw Kiston attempt to lob Van der Sar, only for the keeper to stand his ground and save well.
But it was United who made the breakthrough on 77 minutes when skipper Graeme Murty was desperately unlucky to see his clearance bounce off Lita and straight to Tevez, whose pinpoint cross was caressed home by Rooney.
James Harper was agonisingly close to a deserved equaliser for the home side in the final minute when he raced on to Nicky Shorey's precision pass and clipped a left-foot shot inches wide of Van der Sar's post.
But Reading's endeavours for an equaliser finally came unstitched in stoppage time when Murty's fluffed shot was carried clear by Rooney, who set Ronaldo free to coolly pass the ball beyond Hahnemann and into the bottom corner.