Piotr Trochowski lashed home after 69 seconds and Madrid could not find a response, instead counting themselves lucky that not one but two of their players avoided red cards that could easily have been shown.
Madrid had scored 12 goals combined in their last two visits to Estadio Ramon Sanchez Pizjuan, but only fleetingly threatened the goal here as they looked lost in their own uncertainties for long periods.
Sevilla stunned Madrid in the opening seconds.
Iker Casillas made a mess of a fairly straightforward save to hand Alvaro Negredo a great chance after 40 seconds, the Spain goalkeeper recovering to concede a corner.
But it was from that corner that Trochowski broke free of Angel Di Maria and smashed an unstoppable half-volley high into the net.
Madrid's frustration then threatened to boil over.
Gonzalo Higuain was fortunate to avoid a straight red for kicking out at Fernando Navarro with just three minutes on the clock.
Cristiano Ronaldo was denied twice by Andres Palop, first from a free-kick and then with a shot from the edge of the area that the goalkeeper pushed around the post.
A superb turn gave Higuain space for a shot, but having done the hard work, he blasted high and wide over the target.
But it was far from one-way traffic, and Cicinho tested Casillas with a powerful shot on the angle.
Jesus Navas then shot from a tight angle but it was easy enough for Casillas and the Sevilla winger held up his hand acknowledging he had better options inside.
Navas' speed was causing plenty of problems against the attack-minded Marcelo, and Sevilla had more chances before the break, with Trochowski's shot held by Casillas and Madrid needing to scramble away some dangerous crosses.
Di Maria, booked early on for a late lunge on Negredo, was lucky to make it to half-time with a poor reaction to Ivan Rakitic's challenge going unpunished moments before the break, Rakitic instead earning the caution.
Jose Mourinho instead substituted him at half-time, sending Karim Benzema and Luka Modric out in place of Di Maria and Mesut Ozil.
Modric almost made a fantastic impact in the 52nd minute with a powerful shot that Palop did brilliantly to touch on to the post, with Higuain wasting the chance on the follow-up.
At the other end, Negredo had all sorts of time to line up a shot, only to drag a disappointing effort wide.
Madrid had a glorious chance on the hour mark when Palop failed to deal with Xabi Alonso's free-kick, and Benzema's cross was headed on to the crossbar of an unguarded goal from two yards out.
Higuain then lashed a shot across goal, deflected by Navarro, as they continued to knock on the door. The chances dried up, but it appeared Higuain had given Ronaldo a tap-in with 10 minutes to go before a brilliant last-ditch tackle from Navarro cleared the danger.
Madrid frustrations grew as the clock ticked down but they could not find a chance to seriously test Palop again.