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.
And Real's relentless run stretching back to April last year continued once the action got underway as they scored four times in the opening half-hour.
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.
"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 Frenchman made four changes from the side that saw off Sevilla with ease in midweek with Keylor Navas returning in goal and all of Ronaldo, Benzema and Isco coming in up front.
Once again Zidane was vindicated as all three of the frontline scored in a rapid start.
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.
Real captain for the day Marcelo marked the 10-year anniversary since his debut with a pinpoint cross from which Ronaldo powered home his 17th goal of the season.
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."
Madrid understandably eased off in the second half, but the European champions did net a fifth just before the hour mark when Casemiro was left unmarked to bundle home substitute Rodriguez's free-kick at the back post.
Ronaldo is expected to pick up another individual trophy in FIFA's inaugural The Best award for 2016 on Monday.