Ronaldo's treble - his first since returning to the club in summer - was his second in the Red of United and was the 'perfect' hat-trick of left foot, right foot and a thumping header.
He put Ralf Rangnick's rotated Reds in front with a screamer after 12 minutes and then restored our lead seven minutes before the break after Harry Kane's controversial penalty.
A Harry Maguire own goal pegged us back again but CR7 rose to plant home a header nine minutes from time and United held out for a superb win after last week's derby debacle.
Ronaldo was one of five changes to Rangnick's XI, with Diogo Dalot, Raphael Varane, Nemanja Matic and Marcus Rashford all in ahead of Aaron Wan - Bissaka, Victor Lindelof, Scott McTominay and Anthony Elanga with Bruno Fernandes absent from the squad.
After an opening akin to a chess match in which both sides eyed each other up and felt the opposition out, Ronaldo had an early shot smash into the arm of Eric Dier, but referee Jon Moss bafflingly waved away the claims.
Frustrations did not linger for long, though, with our Portuguese superstar at the centre of things again. Fred's exquisite reverse flick into the path of Ronaldo teed up our no.7 for a shot and he curled home a beauty from 20 yards which gave the stranded Hugo Lloris no chance.
Paul Pogba shimmied and then shot wide, but Antonio Conte's Spurs began to gain a foothold having been distinctly second best for most of the match so far.
It looked as though the north London side had levelled when Ben Davies nipped in to score, only to see his effort chalked out for offside by the linesman.
Spurs came close again on 26 minutes when Son Heung - min picked out Dier from a corner, but his header was hacked to safety off the line by the alert Diogo Dalot. This was a superbly see-sawing contest fully in keeping with its status as a key battle in the race for a Champions League position.
Yet Spurs were - quite literally - given a helping hand when their equaliser came ten minutes before the break. Having had our own penalty appeal waved away, there seemed a sense of injustice when a very similar offence - this time when Dejan Kulusevski's cross came off Alex Telles - was penalised by Moss.
Despite the protests, VAR failed to overturn the on-field call and Kane stepped up to slam home the spot-kick beyond De Gea.
But no sooner had the visitors restored parity, United were ahead again three minutes further on with another tinge of controversy.
Spurs felt Jadon Sancho was offside when he crossed to pick out Ronaldo, but Ronnie's second was rubber-stamped when VAR replays showed Sergio Reguilon had played Sancho onside and the goal stood.
Lloris saved well from Sancho on the cusp of the interval with Old Trafford rocking to the beat of a thrill-a-minute match in which United went in ahead with a more comfortable than it sounds lead.
United kept their probing opponents at arm's length, with only Son's snapshot wide on the turn to show for their renewed intensity.
A hat-trick hunting Ronaldo stung the palms of Lloris from distance and the excellent Fred flashed narrowly off target as Rangnick's side looked to put the game beyond Tottenham's reach.
Victor Lindelof was waiting to come on to help us do that, but before the Swede could be introduced, Spurs had equalised for a second time. If their opener had been contentious, this one was purely fortuitous when Reguilon's cross was turned beyond De Gea by the unfortunate Maguire, on the stretch as he attempted to divert the ball away. In fairness, Maguire had to try and play it with two Spurs players waiting behind him for a tap in.
Lloris saved superbly twice in quick succession as he tipped away Ronaldo's half volley and substitute Edinson Cavani's header.
Time was against the Reds but it was that man again whom came to his side's aid when he completed a stunning hat-trick on 81 minutes. Telles whipped in a flag-kick and Ronnie rose highest to power home a header despite the attentions of Cristian Romero - Old Trafford erupted to greet a goal which makes the superstar the all time world record for goals scored, just the 807.
Lindelof did come on in place of Ronaldo - whom left the field to a loud standing ovation - to tighten the Reds defence in the face of late Spurs pressing as they looked to recover the deficit for a third time.
This time, though, United's game management was good enough to see the game through and, indeed, we could even have had a fourth when Sancho ran through in the final minute only to be snuffed out.
The result moved us back up to fourth, two points ahead of Arsenal (albeit with four games in hand!) and our vanquished capital opponents Spurs, who are three points further back but again with games in hand over us.
Overall team performance: 7/10
United Faithful Man of the Match: Cristiano Ronaldo. Who else..