According to the official FIFA records, Ronaldo's new total of 807 goals sees him overtake Josef Bican's previous record of 805 to stand alone as the game's greatest goalscorer.
United got off to a dream start at Old Trafford, where NFL great Tom Brady was on his feet applauding a moment of magic inside 12 minutes.
Fred flicked a ball on to the returning Ronaldo, who unleashed a thundering 25-yard strike that flew past Hugo Lloris and into the top corner.
talkSPORT co-commentator Dean Ashton reacted: "It was a beautiful flick around the corner from Fred, Ronaldo got it out of his feet and it's a stunning, stinging strike that flashes past Lloris.
"The goalkeeper has got absolutely no chance. A beautiful, beautiful goal from Cristiano Ronaldo.
"You can tell a strike is beautiful when the ball doesn't move after it was hit. Wow."
Tottenham drew level in the 35th minute after referee Jon Moss awarded a penalty.
Alex Telles handled a Dejan Kulusevski cross from the right and Harry Kane stepped up, sending a low strike beyond David De Gea to make it 1-1.
Spurs were not level for long though.
Nemanja Matic put Sancho in behind, with the United forward squaring for Ronaldo to slot home.
The visitors' appeals for offside fell on deaf ears and Sergio Reguilon came in for criticism as the man who kept him on.
Ashton said: "Ronaldo's not going to miss that, he firmly side foots it past Lloris.
"The Tottenham defence stopped, they're all looking up and looking at the linesman.
"The rest of the Spurs defence has caught him offside, but Reguilon was lazy and he was playing him on.
"You can't do that as a full-back, he's not quick enough to react. not good enough."
Tottenham got back on terms again in the 72nd minute.
Antonio Conte's side had looked dangerous from crosses all evening and Reguilon's cross - intended for the offside Cristian Romero - was directed past his own goalkeeper by United skipper Harry Maguire.
Ashton reacted: "If things are going bad for you, they normally get worse before they get better and Harry Maguire is so unfortunate.
"They've played Romero offside, so if Maguire doesn't touch this the Spurs man would be offside.
"But he feels like he has to make the sliding challenge, which inadvertently diverted it past De Gea and in the net."
Thankfully for Maguire though, Ronaldo came to his and United's rescue.
The Portuguese icon powered home a header from a Telles corner to win the game with fewer than ten minutes remaining.
"We've not seen this for a month or so from Cristiano Ronaldo," Ashton exclaimed, "Lips protruding, that arrogant look on his face as if to say, 'It's all about me'.
"He gets up so high and he powers the header into the top corner. Lloris has got no chance.
"Right on the penalty spot, he rises up and BANG - that's the hat-trick.
United did not relinquish their lead for a third time and saw out the 3-2 win.