The Portuguese ace demonstrated the threat he will pose to his former club in their last-16 showdown with a stunning strike in the 26th minute, as his quick feet worked a yard of space outside the box before he unleashed a vicious left-foot drive which arrowed home to leave Beto with no chance.
Jose Mourinho rested a number of his key players with Wednesday's game in mind, but Ronaldo was retained and scored his second of the night early in the second half, with Karim Benzema having given Real the lead from point-blank range with 18 minutes gone.
Ronaldo then tapped in to complete his hat-trick shortly before the hour mark before Mourinho decided to rest his star man for the final 28 minutes, with his name ringing around the Bernabeu as he departed to a standing ovation.
Gonzalo Higuain was harshly dismissed for a second booking in the 66th minute as Real were reduced to 10 men before Manu scored a late consolation for the visitors.
Isco scored twice as Malaga moved back into fourth place in the Primera Division on the back of a 2-1 victory at fellow European hopefuls Levante.
Malaga were looking to avenge last season's 3-0 reverse at the Estadi Ciutat de Valencia but the plan initially went off the rails when Jose Barkero put the home side in front with a 27th-minute penalty.
Isco restored parity through a spot-kick in the 37th minute and then sealed the points with a neat finish just after the restart.
Deportivo La Coruna were pushed closer to relegation from La Liga after a damaging 3-0 home defeat to fellow strugglers Granada.
Carlos Marchena's own goal just before the interval gave the visitors the advantage, which they pressed home early in the second period through Odion Ighalo.
Guilherme Siqueira completed the scoring from the penalty spot in the closing seconds, with Deportivo's misery compounded by the dismissal of Manuel Pablo.
A last-gasp goal by substitute Nelson Valdez allowed Valencia to take all three points from their game with Celta Vigo at Balaidos.
The result is the perfect springboard for Ernesto Valverde's side ahead of their Champions League match with Paris St Germain on Tuesday but it means that the Galicians are condemned to spending another week in the relegation zone.
An injury-time equaliser by Pedro Geromel gave Real Mallorca a vital point against Osasuna at the Iberostar stadium.
Lolo had given the visitors the lead with 15 minutes remaining in the game and looked to have handed Gregorio Manzano the worst possible start to his third spell in charge of the club before the late drama.