Sevilla brought back the big guns who were rested in their narrow win over Huesca, that included Youssef En-Nesyri, Suso and Jesus Navas while Marco Reus, Mahmoud Dahoud and Mateu Morey returned for the Bundesliga side.
Suso gave the hosts an early lead in the seventh minute after cutting inside the box to drill home a strike that deflected in off the outstretched leg of Mats Hummels.
Dahoud levelled matters for Dortmund in the 19th minute with smashing strike into the top corner after Haaland did all the work from a throw-in to get past a couple changes before playing a square pass.
Haaland gave the German side the lead just before the half-hour mark with a toe-poke past the onrushing goalkeeper Yassine Bounou.
The Norwegian gave Dortmund a two-goal cushion just before the break with a well-placed shot past Bounou after Reus raced clear on the counter-attack and played the ball on the platter.
Sevilla were struggling to raise their game coming from the break, as Jude Bellingham almost made added a fourth for Edin Terzic's charges in the last 20 minutes with a volleyed effort from the edge of the box that was parried away by Bounou.
However, Oscar Rodriguez came close to pulling a goal back for Julen Lopetegui's men three minutes later with a free-kick from 25-yards out that crashed the post and ricocheted into the hand of the diving goalkeeper Marwin Hitz and away from the goal-line.
Luuk de Jong managed to reduce the deficit six minutes before time with a thumping volley at the back post after a cross by Rodriguez, giving the Europa League winners some hope heading to the second leg.