The game had been relatively even for nearly the whole of the first half when the controversial Portugal international broke into the box and went down under Steed Malbranque's challenge.
Replays showed there was no contact, but referee Mark Clattenburg gave the penalty and the goal knocked the stuffing out of Spurs.
They had got off to a bright start and seemed more than willing to attack the Premiership leaders early on.
But it was United that seemed more likely to score whenever they moved forward, and they should have done so on 24 minutes.
A Ryan Giggs corner was met by Nemanja Vidic and Michael Carrick forced a save out of Paul Robinson. The ball then fell to Ronaldo, of all people, just six yards out, but he blasted well over the bar.
Sir Alex Ferguson's men continued to press and should have had a penalty earlier than they eventually did on 29 minutes.
Henrik Larsson was brought down by Anthony Gardner in the box, but Clattenburg was unmoved. It seemed to be a much better penalty shout than the one which was eventually given.
However, Spurs had their best chance four minutes later when Dimitar Berbatov, returning from a groin injury, got across Rio Ferdinand and forced a finger-tip save out of Edwin Van der Sar.
But the home fans' optimism was to be short-lived as Ronaldo won his penalty and converted it superbly on the stroke of half-time.
White Hart Lane's big screens revealed to home fans that the winger had dived, and he was to receive a torrent of abuse throughout the second half.
But this only served to spur him on to produce a majestic display, as he began to show the form which makes him hot favourite to win the Player of the Year award.
However, it was Serbian defender Vidic who was arguably United's best performer on the day, and he was rewarded with a goal on 48 minutes.
He had forced a fingertip save from Robinson with a shot from the edge of the box moments before and, after Carrick forced another corner, Vidic was on hand to send a bullet header home.
Then came the moment of the match from Ronaldo that killed the game off once and for all.
His trademark quick feet were all it took for him to beat Young-Pyo Lee and race to the by-line where he picked out Paul Scholes inches out for a tap-in and the three points.
Ronaldo was replaced by Ji-Sung Park on 68 minutes to a chorus of boos - but he had done his job once again.
Berbatov had another great chance to reduce to the deficit after being played through by Tom Huddlestone, but he fired straight at Van der Sar.
The Bulgarian also tried to win a penalty of his own under a challenge from Ferdinand, but his dive was even more cynical than Ronaldo's.
With a quarter-of-an-hour left, Berbatov forced another fine save from Van der Sar with a header, but Giggs made it 4-0 moments later after latching on to a Louis Saha pass, making it a humiliating scoreline for Spurs.