Sevilla leapfrogged Barca into second, four points behind Real, thanks to Wissam Ben Yedder's hat-trick in a hugely impressive 4-0 win at sixth-placed Real Sociedad, whilst Atletico Madrid won 2-0 at Eibar to move up to fourth.
At the Bernabeu, Ronaldo was honoured by previous Ballon d'Or winners to have played for Madrid including Luis Figo, Ronaldo, Michael Owen and his coach Zinedine Zidane before kick-off.
Isco and Karim Benzema slotted home from close range before Ronaldo, who had been rested for Real's 3-0 Copa del Rey win over Sevilla in midweek, bulleted home a header from Marcelo's cross.
Another simple finish from Isco made it four before the break and Casemiro turned home James Rodriguez's free-kick for the fifth after half-time. Barca can close back to within three points of the leaders with victory at Villarreal on Sunday.
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"There is no limit, but on the other hand we have to do everything possible to make sure it lasts," Zidane said of his side's stunning form.
The hosts got a break for the opener as Isco could have been penalised for a trip on Sergi Samper before he exchanged passes with Benzema and slotted low past Guillermo Ochoa.
Madrid were also fortunate for the second as Benzema appeared offside when he prodded into an empty net after Ochoa tamely parried Luka Modric's shot into his path.
And with the Granada defence once again pulled apart by Madrid's movement, Modric's low cross found an unmarked Isco for a simple finish at the back post for his second of the afternoon.
"The matches are prepared in a certain way depending on whether we have two, three or four days, but the idea is always to do our best, be physically ready and concentrated," added Zidane.
"If we are ready and concentrated we can do great things."
Ronaldo is expected to pick up another individual trophy in FIFA's inaugural The Best award for 2016 on Monday, but one of his rivals for the prize ended a three-month goal drought in La Liga as Antoine Griezmann sealed Atletico's 2-0 win at Eibar.
After a first-half short on goal mouth action, Saul Niguez nodded Atletico in front eight minutes after the break.
Griezmann hadn't netted in 821 La Liga minutes since October 2, but bundled home from close range after a one-two with Kevin Gameiro 16 minutes from time. However, it is Sevilla who are Real's closest challengers as they bounced back in style from their midweek mauling to inflict Sociedad's first home defeat since the opening day of the season.
And despite en early rally by Sociedad at the start of the second period, Ben Yedder then teed up Pablo Sarabia to kill the game 17 minutes from time.
Ben Yedder produced another cool finish to complete his first La Liga hat-trick in the closing stages and take his tally for the season to an impressive 15.