The Portuguese star added a second-half penalty and tap-in to his early free-kick, as Los Blancos earned all three points in what was the final clash between these two sides at Atelti's Vicente Calderon stadium.
Next season, Atletico will move to Estadio La Peineta -- the Olympic Stadium on the outskirts of Madrid -- as it leaves its historic 50-year-old home.
Diego Simeone had urged his players to leave a lasting legacy but, in truth, they were uncharacteristically toothless as Ronaldo and Real romped to victory.
Zidane and his players have been self-critical of their performances in the opening stages of matches this season, often citing a "lack of intensity" for early setbacks.
But it was Real's blistering start that put it on the front foot, something Simeone highlighted as the decisive factor in his post-match press conference.
"Well, the result is what it is," he started somewhat philosophically. "It's clear that, especially in the first half, Real was better than us and had more chances to score.
"In the first 20 minutes of the second half, we were better, had chances to score, played in Real's half and controlled the game.
"Afterwards, the penalty broke our dreams of getting back into the game."
There was some debate as to whether Real's opening goal should have been given to Ronaldo or Raphael Varane.
Ronaldo's strike hit the French defender in the wall, wrong-footing Jan Oblak in the Atelti goal to give Real the lead.
Despite Atletico dominating the opening stages of the second half, Stefan Savic made a hash of a long ball and his clumsy foul on Ronaldo gave referee David Fernandez no choice but to point to the spot.
Ronaldo stepped up and sent Oblak the wrong way to double the visitor's lead.
With Atletico pressing for a route back into the match, they were susceptible to the counter-attack.
Indeed, it was a long ball into Gareth Bale's path that led to its third goal, the Welshman squaring for Ronaldo to tap into an empty net and silence the Calderon for the last time.
In La Liga's early kick-off, Barcelona -- without the sick Lionel Messi and suspended Luis Suarez -- limped to a goalless draw at home to Malaga as it lost more ground on Real.
Despite Malaga finishing the match with nine men, Barcelona was unable to make the breakthrough and now finds itself four points behind Real at the top of the table.
Meanwhile, Jorge Sampaoli's Sevilla completed a stunning comeback to stay within reach of the summit of La Liga.
After finding itself two goals down away at Deportivo La Coruna, Steven Nzonzi's goal just before the break reignited hope.
Spanish international Vitolo found the equalizer three minutes from time, before Gabriel Mercado's scrappy 94th-minute goal earned it the win.
In Germany, Borussia Dortmund hauled itself back into the Bundesliga title race with a 1-0 victory over Bayern Munich.
Newly-promoted RB Leipzig continues to surprise and sits top, three points clear of Bayern, with Dortmund a further three behind.