Ronaldo now has 120 United goals to his name, but scored his first since leaving for Real Madrid 12 years ago to take Ole Gunnar Solskjaer’s men top of the Premier League table.
United were made to work harder than expected for the three points, but were able to rely on Ronaldo’s predatory instincts to strike twice either side of Javier Manquillo’s well-worked equaliser.
Bruno Fernandes then sealed a day where Portuguese stars shone with a stunning long-range effort 10 minutes from time before Jesse Lingard rounded off the scoring in stoppage time.
United’s fortunes on the field have declined dramatically since Ronaldo’s departure with no Premier League or Champions League success since Alex Ferguson retired as manager in 2013.
His return was enough to generate a feverish atmosphere among 74,000 in attendance not seen at Old Trafford for many years.
The 36-year-old was serenaded with songs in his honour long before kick-off and even received celebrations of the goals he scored in a shooting drill in the warm-up.
Ronaldo’s arrival has added even more firepower to an already loaded selection of attacking options on offer to Solskjaer.
Jadon Sancho and Mason Greenwood flanked Ronaldo in a front three with Fernandes and Paul Pogba supplying the ammunition from midfield.
The crowd who had come for a party were starting to get restless as Newcastle held out relatively comfortably until Ronaldo’s first big moment arrived in first-half stoppage time.
Greenwood had scored in all of United’s first three Premier League games before the international break and provided the spark once more as Freddie Woodman spilled his deflected effort and the ball fell perfectly for Ronaldo to smash home.
Rather than opening the floodgates for a comfortable win, Newcastle emerged for the second-half with a far more potent threat and cut United open to stun the home support 10 minutes into the second-half.
Miguel Almiron, who was only cleared to play on Friday after the Paraguayan football federation withdrew a case for him to be banned for not being released for international duty, burst through midfield and released Allan Saint-Maximin.
The Frenchman then rolled the ball perfectly into the path of Manquillo to slot home his first Newcastle goal in 85 appearances.
United on the other hand now have one of the deadliest finishers in the history of the game and Ronaldo ensured the day would be all about him on 62 minutes.
Despite his advancing years, Ronaldo showed no shortage of pace to burst away from Isaac Hayden to latch onto Luke Shaw’s pass and his powerful strike went straight through Woodman’s grasp.
United still needed the intervention of David de Gea to secure the win as the Spaniard brilliantly turned behind Joelinton’s shot that was destined for the top corner.
Fernandes has been United’s talisman for the majority of the 20 months since he joined from Sporting Lisbon, just as Ronaldo did in 2003.
And the midfielder ensured he was not completely overshadowed by his compatriot with a sensational strike into the top corner from Paul Pogba’s pass.
Pogba was also involved in the fourth as Lingard turned onto his pass and curled into the far corner.