The Portugal forward opened the scoring with a deflected free-kick that wrong-footed Atletico goalkeeper Jan Oblak.
Ronaldo added a second from the penalty spot before he completed his treble when he tapped in Gareth Bale's cross.
Real now have a four-point lead over second-placed Barcelona, who were held to a goalless draw by Malaga earlier.
Ronaldo has scored eight La Liga goals for the European champions this season, to draw level with Barcelona duo Lionel Messi and Luis Suarez.
The 31-year-old's treble also saw him go one goal of clear of legendary Real forward Alfredo Di Stefano's individual total of 17 goals in the Madrid derby.
His total could have been more had Oblak not produced a stunning diving save to keep out Ronaldo's powerful header when the scoreline was goalless.
The result - in what was the last Madrid derby at the Vicente Calderon in La Liga - was also a blow to Atletico's title hopes with Diego Simeone's side now nine points adrift of Real.
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