The defending champion set the tone from the start as Tiago Cardoso and substitute Saul Niguez scored early before Antoine Griezmann and Mario Mandzukic sealed Atletico's most lopsided victory over Madrid since 1987.

It was also Madrid's biggest defeat to any opponent since a 5-0 loss to Barcelona in 2010.

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The return of Ballon d'Or winner Cristiano Ronaldo didn't help an injury-hit Madrid, which also got poor showings from its other star players at Vicente Calderon Stadium.

"We played poorly from start to finish. Nothing worked. It's a day to forget," Ronaldo said. "Madrid can't lose to any team 4-0."

Diego Simeone's side extended its undefeated streak against Madrid to six meetings since losing last season's Champions League final in extra time. Atletico has outscored Madrid 12-4 in the undefeated run.

Atletico may have had more important victories over its fiercest rival since ending Madrid's 14-year unbeaten domination of their contests in the 2013 Copa del Rey final, but it had yet to beat Madrid at home in the league since the 1998-99 season.

Simeone, however, downplayed the significance of a win its fans will relish for years to come.

"It's just another league match," Simeone said. "We have our philosophy of going forward one game at a time, partly because we don't know any other way."

Atletico pulled to within four points of Madrid. Barcelona also trails Madrid by four before visiting Athletic Bilbao on Sunday.

Villarreal moved to one point off fourth place and the last Champions League spot by beating Granada 2-0.

David Barral also scored a hat trick to help Levante escape last place with a 4-1 comeback win over Malaga, while Manuel "Nolito" Agudo leveled with five to play to salvage Celta Vigo a 1-1 draw at Real Sociedad.

Madrid was without injured first-choice players such as James Rodriguez, Sergio Ramos, Pepe and Luka Modric, while Marcelo was suspended. But it still had enough star power with Ronaldo back from a two-match ban for kicking an opponent, along with Gareth Bale, Karim Benzema, and midfield pair Toni Kroos and Francisco "Isco" Alarcon.

None of them could hold back the red-and-white tide.

"Atletico beat us in every facet. We didn't have a player who had a good game," Madrid coach Carlo Ancelotti said. "This is the worst game by my team since I have been coach."

Since finishing 2014 on a Spanish record 22-win streak, Madrid has been eliminated by Atletico from the Copa del Rey, and beaten a second time in the league this season.

Benzema called the defeat "a disaster." Several Madrid players asked their fans for "forgiveness."

While Atletico overpowered Madrid in the midfield '€” even after it lost playmaker Jorge "Koke" Resurreccion to a leg injury in the eighth minute '€” it picked the visitors apart on the wings.

Atletico's first goal in the 12th started when right back Juanfran Torres broke down the flank to send in a cross that was flicked on to Mandzukic. The striker spotted Tiago arriving in a second wave, and he used one touch to drill his strike through the hands of goalkeeper Iker Casillas, who could have done more to keep the ball out.

"Everything went our way from the first minute and we didn't give Madrid a chance," Tiago said. "Our coach again has been boosted because everything he said came to pass. He told us to find spaces to attack Madrid behind its defense and that's what happened."

Four minutes later, Madrid was overrun on the left as Siqueira dribbled to the endline before crossing for Niguez to stun both his teammates and opponents with an acrobatic bicycle kick that sent the ball in off the post.

Atletico went close to a third goal on four occasions before Griezmann beat Raphael Varane to the far post, where he tapped in Niguez's headed pass in the 67th.

Mandzukic polished the result in the 89th when he headed in substitute Fernando Torres' cross. (**)

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