Spurs made a perfect start in the Sanchez Pizjuan as Dimitar Berbatov played in Robbie Keane in just the second minute and the Irishman slotted home the rebound after keeper Andres Palop had blocked his initial shot.
The home side drew level with 19 minutes on the clock when referee Mr Hamer harshly adjudged that Paul Robinson had brought down Adriano in the area, despite the England international clearly playing the ball. Former Spurs striker Freddie Kanoute confidently converted the spot-kick.
Robinson parried further efforts from Jesus Navas and Kanoute as Sevilla began to dictate play and the home side were ahead nine minutes before the break.
Navas managed to hook in a cross from the right, Julien Escude headed the ball back from beyond the far post and Alexander Kerzhakov nodded home from six yards out.
The second half was slightly less dramatic than the first, with Keane firing narrowly wide just before the hour mark.
Soon after, Kanoute screwed his shot wide of the near post after good link-up play down the left flank between David and Adriano.
Kanoute spurned another opening 15 minutes from time, before Spurs sub Steed Malbranque passed up a chance to level the scores with five minutes to play, following good work by Keane.
Sadly the game also saw some disturbances among the travelling fans, but the Spurs faithful left knowing that their side are still in with a fair chance of reaching the semi-finals.