The Portuguese forward, who became the world's most expensive player when he joined Real from United in 2009, set up Karim Benzema to open the scoring from close range in the 18th minute at a festive Bernabeu stadium.
Ronaldo doubled the home side's lead with a powerful left-foot strike from the edge of the area eight minutes later and added his second in the 46th minute after a blunder in the Sevilla defence.
"We have a phenomenon [in Ronaldo]. I cannot recall anything like it," Real director and former club great Emilio Butragueno told Canal Plus television.
"It seems normal for him to score three goals and we continue to enjoy his performances."
Real forward Gonzalo Higuain was sent off midway through the second half for a second yellow card but it did little to sour the party atmosphere ahead of United's visit in a last 16 first leg tie.
Ronaldo was substituted to a rousing ovation shortly before Higuain's dismissal and Sevilla's misery was compounded with 10 minutes left when Hedwiges Maduro picked up a second yellow.
"It has been a really nice week but we can't stop here," Isco told reporters. "We have to keep fighting because this team has a chance to qualify for the Champions League.
"We are fourth and have our fate in our own hands."
Valencia's Nelson Valdez came off the bench to snatch a last-gasp goal in a 1-0 win at Celta Vigo that give his side a boost before they host Paris Saint-Germain in the Champions League on Tuesday.
Celta held Ernesto Valverde's team at bay until the third minute of added time when Joao Pereira floated a cross to the back post and Valdez, who had only been on the pitch a few minutes, nodded powerfully past Javi Varas.
