The Portuguese forward was unavailable last weekend in the Manchester derby due to a hip flexor injury, but he bounced back with a hat-trick and the winning goal.
United may have been without Bruno Fernandes, who missed the game through illness, but Fred’s flicks were the substitute and that’s how the home side took the lead early in the first half.
The Brazilian – who is enjoying a fine start to 2022 with five goal involvements in his last 10 Premier League games – clipped a pass into the middle of the park for the Portuguese striker to blast past Hugo Lloris.
Antonio Conte's Spurs were very good and deserved at least a point from the game but their defensive struggles held them back, like it has done all season.
Spurs looked the more likely to go and grab the winner late on but when Ronaldo is on the pitch, that slightly tips the odds in United's favour.
Alex Telles' inswinging corner was met by the head of Ronaldo who rose above Matt Doherty and seal the three points for the hosts.
Story of the game
Despite a relatively bright start from the visitors, it was the hosts who had the earliest opportunity which came after a wonderful piece of skill from Jadon Sancho.
Harry Maguire picked the English winger out and Sancho’s first touch was simply perfect to take it around Matt Doherty. Sancho then found Ronaldo in the area whose strike struck the back of Eric Dier’s arm. Ronaldo led the protests, John Moss waved play on.
Minutes later, Ronaldo served up a special strike from distance to beat Lloris. It was stunning and was reminiscent of his famous goal against Porto over a decade ago.
Tottenham thought they had bounced back immediately when Ben Davies turned a cute finish round David De Gea, but the linesman had his flag up.
They then got the equaliser they deserved when Dejan Kulusevski’s cross was blocked by Alex Telles’ arm inside the penalty area. The Brazilian could have no complaints about the handball decision, it was certainly an unnatural position and Jon Moss awarded a penalty.
Up stepped Kane and he smashed it past De Gea with conviction into the bottom left corner.
But United came right back at Spurs and found themselves ahead once again, through Ronaldo (again). And it was Nemanja Matic who started it with an excellent lobbed pass over Spurs’ backline to pick out Sancho.
Sergio Reguilón was caught stepping up too slow to try and catch Sancho offside, but the English winger remained on before slotting the ball across to Ronaldo who hammered home.
Tom Brady was in the house to watch both Kane and Ronaldo. The Spurs forward has been open with how much he idolises the most successful NFL player in history.
On the hour mark, Spurs created yet another glorious opportunity. It was kickstarted by Pierre-Emile Højbjerg who picked up Sancho's loose pass. The Danish midfielder slung a ball into Kane who flicked it wide for Kulusevski to dribble at Telles, he cut the ball back to Son whose curled effort went narrowly wide.
With Spurs pushing forward for an equaliser, Rangnick made changes as he brought on Anthony Elanga for Marcus Rashford. Rashford, who hasn't been in the best of form in recent weeks, received warm applause from the fans and he showed his appreciation.
Just as the United boss was about to make his second change and bring on Victor Lindelof, Maguire turned the ball past De Gea.
United may be disappointed that VAR didn't intervene as Reguilón's cross was headed towards an offside Cristian Romero. Maguire slid in to clear the ball away from Romero which ultimately ended in the back of his own net.
With 20 minutes to play, the game was well poised for either side to find a winner.
But it was Ronaldo who had the final say as he headed home from a Telles corner.
They come to Manchester on Tuesday night for the second leg tie of the Round of 16 in the Champions League.
Will history repeat itself? Stay tuned for another episode of this fairytale comeback story.