Real beat Atletico 2-0 at the Calderon
Real captain Raul lived up to his reputation as Atletico's bogey player when he scored his 11th goal against them in city derbies, steering in at the near post with just over 30 seconds on the clock.
Van Nistelrooy scored the second against the run of play and took his tally for the season to 12 when he clipped home from a corner two minutes from the break.
"It wasn't a spectacular victory, but it was a necessary one," said Real coach Bernd Schuster. "What I'm pleased about is that we are working as hard as every other team, but the quality we have means we are a cut above all our rivals."
Real's seventh league win in a row kept them seven points clear of Barcelona who claimed a flattering 1-0 win over a well organised Racing Santander at the Nou Camp. Thierry Henry scored the winner with an opportunist header in the first half.
Villarreal are in third spot, five behind Barca, after their 3-0 win over Valencia on Saturday, while Atletico are a further point back in fourth.
Earlier, Valladolid striker Joseba Llorente got his name in the record books when he scored the fastest goal in Primera Liga history, putting his side in front in their 2-1 win over Espanyol with just seven seconds on the clock.
The Madrid derby followed the now familiar pattern of recent years with a nerve-riddled Atletico paying the price for defensive errors and failing to take advantage of their chances while Real gave their neighbours a lesson in finishing.
Atletico have not beaten Real since October 1999 and claimed their last win over them at the Calderon in June of the same year.
Real could hardly have got off to a better start. Raul poked in from close range in the first attack of the game after Robinho had dispossessed centre-back Pablo Ibanez on the byline and slipped the ball towards the near post.
Roared on by their fervent home support, Atletico proceeded to lay siege to the Real area, but they were unable to find a way past an inspired Casillas.
The Real keeper denied Diego Forlan with an out-stretched foot, produced another great reaction save to scoop a Raul Garcia header off the line and tipped two Sergio Aguero shots over the bar.
Midfielder Thiago Motta also sent a thundering header against the woodwork, but the Atletico pressure was to no avail and Real extended their lead just before the break through Van Nistelrooy.
Atletico had a strong penalty appeal turned down early in the second half when Michel Salgado clipped Aguero's ankle as he jinked into the area, but they faded after that and Real ran out comfortable winners.