Matches against Sevilla have proved rich pickings for Ronaldo and it was no different on Saturday as he followed up Karim Benzema's 18th-minute opener with goals in the 26th, 46th and 59th minutes as Madrid sauntered to victory .
That took his tally of hat-tricks for the Spanish giants to an incredible 20 before he was replaced in the 63rd minute as Jose Mourinho opted to wrap his trump card in cotton wool ahead of Wednesday's visit of United in the first leg of the Champions League last-16 clash.
Soon after Ronaldo's departure Madrid were reduced to 10 men when striker Gonzalo Higuain was sent off but Sevilla also finished with a men less after losing Hedwiges Maduro to a red card with nine minutes left.
Sevilla did net a late consolation through Manu del Moral but it mattered little as Mourinho's men, who surprisingly lost to Granada last week, trimmed the gap to leaders Barcelona back to 13 points, the pacesetters playing Getafe on Sunday.
Ronaldo always seemed likely to find the back of the net on Saturday having struck a hat-trick in last season's corresponding fixture against Sevilla and four away from home against the same opponents the previous campaign.
However, he was happy to play creator for Madrid's opener on Saturday, his low cross being turned home by Benzema, although not without a large slice of luck.
The France striker looked to have missed the opportunity as the ball deflected away from goal off his foot, but it hit covering defender Fernando Navarro before rolling back to Benzema standing on the line, and he had the simply task of tapping home.
It did not take Ronaldo much longer to get his name on the scoresheet though, the £80million signing from United in 2009 lashing home an unstoppable left-footed shot from 25 yards out.
Former Madrid winger Jose Antonio Reyes had a chance to halve the deficit in the 32nd minute but Diego Lopez - who recently rejoined the capital club from Sevilla following an injury to Iker Casillas - saved down by his right-hand post.
Ronaldo showed his free-kick prowess in the 43rd minute with an effort which Beto batted away after it had bounced up awkwardly, and the visiting keeper then did well to keep out Sergio Ramos' header from a corner.
Beto was left with no chance, though, as Ronaldo made the most of a poor defensive misjudgment from Federico Fazio to make it 3-0 less than a minute into the second half.
Fazio allowed a high ball to bounce over his head and Ronaldo stole in behind before drilling a low shot past Beto into the far corner.
The world's most expensive player then completed his treble 13 minutes later with a close-range finish following Higuain's pass across goal.
That proved to be one of last contributions Ronaldo made as he was replaced to a standing ovation from the home fans soon after, while Higuain's involvement in the game did not last much longer either - although for completely different reasons.
The Argentina international was shown a second yellow card for tripping Navarro.
Alvaro Negredo had a couple of decent efforts as Sevilla tried to pull a goal back, but Madrid's defence - with the fit-again Pepe appearing as a second-half substitute - held firm and the visitors lost their man advantage when Maduro picked up a second yellow for a foul on Michael Essien.
Despite that, Sevilla did manage to net when Manu fired home in the 87th minute, though it was no more than a consolation.