Real Madrid's 40-game unbeaten run has come to an end after Stevan Jovetic's stoppage-time strike saw Sevilla come from behind to beat the European champions.
After a quiet opening to the game, the hosts almost took the lead from Samir Nasri's corner on 19 minutes, which was met by Steven N'Zonzi, but the midfielder was unable to keep his header down.
Real also went close midway through the first half when Cristiano Ronaldo found space on the left flank and tried to find the far corner of the net before his strike was gathered by Sergio Rico.
Ronaldo wasted another chance just before the break when Karim Benzema teed up the Portuguese frontman, who scuffed his effort wide of the target.
Wissam Ben Yedder tried to give the hosts the lead after the break, but saw his low drive blocked by Keylor Navas.
Real were awarded a penalty just after the hour mark when Ronaldo raced into the area before drawing a foul from the onrushing Rico.
When the FIFA World Player of the Year stepped up to send Rico the wrong way and score, Real seemed destined for a 41st match without defeat.
However, their fortune changed when Pablo Sarabia's free kick was headed into his own net by Sergio Ramos with six minutes left.
Sevilla then secured the points when Jovetic seized on Sergio Escudero's pass before curling a 25-yard shot beyond the reach of Navas.