Arsenal had already wrapped up a place in the knockout stages, but victory in Spain would have ensured that they finished top of Group H as well.
Arsene Wenger gave a few senior players a rest, with the likes of Nicklas Bendtner, Justin Hoyte and Armand Traore handed rare starts.
Freddie Kanoute had the first chance of the game five minutes in, but shot well over from 15 yards out and the Gunners took the lead six minutes later.
Bendtner found space down the right and his cross to the far post was controlled well by Eduardo, who kept his cool to beat keeper Andres Palop with a low shot.
Arsenal then began to dominate the play, but midway through the half Sevilla were level as a ball in from the right was only half-cleared and Seydou Keita drove home a superb left-foot shot from just outside the area.
Ten minutes later it was 2-1 to the home side after Jesus Navas had won a free-kick on the right for an extravagant dive.
Dani Alves played in the set-piece to the near post and Luis Fabiano glanced his header past Manuel Almunia into the far corner of the net.
Straight after the restart Dani Alves played in Fabiano, but he wasted a chance to get a shot in on goal as Philippe Senderos came across to cover.
Just before the hour mark Alves' ball in from the right was poked narrowly wide of the far post by Fabiano, with Almunia scrambling across his line.
Tempers became frayed as time ticked away, with Wenger ordered to the stands, but choosing to stand just behind the dugouts after a clash with the fourth official.
Right at the death Sevilla made the game safe as Kanoute went down in the area under the challenge of Kolo Toure and Bacary Sagna and the referee awarded a penalty.
Kanoute got up to take the spot-kick himself and drilled the ball low into the corner of the net with Almunia rooted to the spot to make the final score 3-1.