Ronaldo extended his lead as the all-time top scorer in Madrid derby matches by taking his tally to 21 and put Real firmly on course to defend their title in the final in Cardiff on June 3rd.
The Portuguese rewarded a bright Real start by heading home Casemiro's deflected cross after just 10 minutes.
Ronaldo then smashed home from just inside the area and turned home Lucas Vazquez's cross in the final 20 minutes as Real continued their domination of Atletico having eliminated them in the Champions League for the past three seasons.
"The team was tremendous. I scored the goals but the team was phenomenal from start to finish," said Ronaldo.
The sides meet again for the second leg on May 10th.
"We have a good advantage but the tie isn't over yet," added Ronaldo.
"Atletico are a good side and it is not a coincidence they are in the semi-finals again. We have to be concentrated next Wednesday."
Atletico boss Diego Simeone, meanwhile, told his side to forget their latest derby demolition and hope for a miracle at the last European match at their Vicente Calderon stadium next week.
"We need to forget about this game," said the Argentine.
"It seems impossible, but it is football and football has these unexpected things that make it marvellous.
"Until the last drip of hope is gone, we will give it everything we have."
Real needed a stoppage time equaliser en route to beating Atletico in the 2014 final, scored a late winner in the quarter-finals a year later and edged last season's final between the two on a penalty shootout.
However, there was far more a gulf between the sides this time round.
Real piled on the pain in the opening stages for the 4,000 visiting away fans and could have killed the tie in the opening half hour.
Atletico were handed a lucky escape on seven minutes when Jan Oblak parried Dani Carvajal's effort at the end of a careering run and the Slovenian recovered to also turn behind Karim Benzema's follow-up effort.
No let off
There was no let off three minutes later, though, as Atletico failed to clear a corner and Casemiro's bouncing cross looped up for Ronaldo to power home a header.
Oblak kept Atletico alive in the moments that followed with a brilliant save from Raphael Varane's header and more comfortable stop from Isco.
However, at the other end, Keylor Navas rescued Real from conceding a vital away goal when he got a touch on the ball as Kevin Gameiro tried to round him when clean through on goal.
The majority of the efforts continued to rain down on Oblak's goal as Luka Modric drilled a shot from the edge of the box inches wide.
And Benzema then acrobatically turned a Ronaldo cross just over the bar. The only negative news of the night for Real was an injury to right-back Dani Carvajal just before half-time as he pulled up with a muscle problem that looks set to keep him out of the second leg.
Clear-cut chances were far harder to come by after half-time as Atletico toiled to create, whilst Real sat on their lead waiting for the chance to counter-attack.
However, once again in ties between these two, Real got the slice of luck to go with their extra quality.
The ball rebounded up perfectly off the heels of Filipe Luis for Ronaldo to blast high past Oblak.
And Ronaldo completed his second hat-trick against Atletico this season four minutes from time when Lucas Vazquez's cutback picked out the four-time World Player of the Year to slot home from close range.
By Kieran Canning / AFP