Atletico Madrid slumped to a stunning 3-0 loss at Osasuna on Sunday, leaving Real Madrid as the sole leader of the Spanish league for the first time since May 2012.
Osasuna beat Atletico at its own game, both in its tough, physical approach and its set piece strategy to take a three-goal lead at the break after one of Atletico's worst first halves in three years under coach Diego Simeone.
Alvaro Cejudo opened the scoring from a corner kick in the sixth minute before fellow forwards Emiliano Armenteros and Roberto Torres added goals in the 21st and 42nd.
Atletico's loss came one day after Barcelona lost 3-1 at Real Sociedad, with both the former front-runners looking weary after their Champions League trips in midweek.
Atletico fullback Filipe Luis, who returned from injury, said that their win at AC Milan on Wednesday had nothing to do with this defeat.
"Osasuna played a great game," said Filipe Luis. "You can't take anything away from them. They beat us in every facet of the match."
Atletico and Barcelona have both dropped 10 points over the last seven rounds, allowing Madrid to turn a five-point deficit into a three-point lead despite playing without Ballon d'Or winner Cristiano Ronaldo during a three-game suspension. Madrid hadn't topped the standings since winning the title in 2011-12.
Simeone quickly needs to restore both his team's fitness and confidence before it hosts Madrid next weekend after its crosstown rivals travel to German side Schalke 04 on Wednesday.
Also on Sunday, Athletic Bilbao strengthened its hold on fourth place by winning 2-0 at Real Betis after the bottom side had two players dismissed, while Valencia and Sevilla won to move to within five points of sixth place and Spain's last Europa League spot.
Osasuna had already earned draws against Barcelona and Madrid at El Reyno de Navarra Stadium this season, and Javi Gracia's side lived up to its reputation as being one of the toughest hosts in the Liga.
"I think the fact that those three teams haven't won here says a lot," said Cejudo, who credited his team's fans for their vocal support that he said "pushes" the team forward.
Osasuna used a bit of well-executed trickery to strike first when it sent several players to the near post to draw in Atletico's defence before Torres crossed to the far post, where Cejudo had charged in late to drive the ball home.
Osasuna was a step faster to almost every ball and Armenteros beat Gabi Fernandez to a loose ball before he unleashed a blistering left-footed strike from outside the area that went in off the post.
Diego Costa mustered a shot that sailed wide in the 21st, but Atletico never responded to Osasuna's surge and a collective breakdown in defence cost it a third goal. David Villa first failed to fight for a ball in midfield, and then two defenders left Torres unmarked to nod Damia Abella's cross under goalkeeper Thibaut Courtois.
"It was a day to remember," said Gracia. "It's a big step for us as we try to stay up."
Bilbao's first victory in four rounds lifted it four points clear of Real Sociedad and kept it in command of Spain's last Champions League berth for next season.
In contrast, Betis was left 11 points from safety after a dismal performance that at times bordered on self-destruction amid some questionable refereeing decisions.
Bilbao's Iker Muniain converted a penalty in the 34th minute after Damien Perquis tripped Kike Sola in the area.
Another reckless tackle by Perquis earned him a second yellow card in the 41st to completely deflate the crowd at Benito Villamarin Stadium. Betis was left with nine men from the 58th when Lorenzo Reyes handled the ball after he had already been booked for arguing.
Bilbao substitute Guillermo Fernandez headed in the first ball he touched in the 81st.
Valencia needed an injury-time goal from 19-year-old defender Ruben Vezo in his first start to complete a 2-1 comeback win at home over Granada.
Sevilla won 1-0 at Rayo Vallecano thanks to fullback Jorge "Coke" Andujar's 57th-minute header. Sevilla played the last seven minutes with 10 men after Vicente Iborra received his second booking.