Karim Adeyemi’s superb strike in the second half was enough for Dortmund to down Chelsea at Signal Iduna Park and take a lead into the second leg at Stamford Bridge.
The Blues looked stronger for much of the match, having more chances and more on target, but the closest they came to a goal was when Joao Felix hit the crossbar in the first half.
It was Adeyemi’s strike that gave Dortmund the win in the 63rd minute, while Chelsea’s efforts, including a Kalidou Koulibaly chance which was cleared off the line and a saved Enzo Fernandez shot late on, didn’t manage to find the net.
It is the first time since 2016 that Dortmund, who now have seven successive victories across all competitions, have beaten Premier League opposition in Europe.
Dortmund started well but Chelsea were able to stave off the initial pressure before Mykhailo Mudryk tried to get the Blues started on the counter, breaking into the area before being denied by a good sliding tackle from Nico Schlotterbeck.
Chelsea could not make anything of two corners in quick succession but thought they gone ahead on a set piece soon after when Reece James sent a free kick into the area and it deflected off Thiago Silva and in, but a VAR check ruled it out for handball by the Brazilian.
Dortmund could have taken the lead when Sebastien Haller, making his first European start for the hosts after recently returning to action after overcoming testicular cancer, was unleashed by Julian Brandt but blasted an effort into the right side netting from the right of the area.
James’ free-kick was diligently nodded away but the ball bounced back in the Blues’ favour and eventually landed at the feet of Felix, who fired a close-range effort directly at goalkeeper Gregor Kobel.
Adeyemi skied an effort for the hosts before Chelsea had their best chance of the first period as Felix latched onto Kai Havertz’s cross at the left side of the area but his strike cannoned back off the crossbar.
Marius Wolf misdirected a powerful effort to ensure it was goalless at the break.
Kobel kept out a Blues corner after the restart but the visitors piled on the pressure and won another free kick when James was brought down by Can before directing his effort at the top corner where it was met by a fine leaping stop from Kobel.
The Dortmund keeper was called into action again when James played a one-two with Ziyech and fired on goal but watched Kobel tip his effort away.
Dortmund finally took the lead through Adeyemi’s sensational solo run.
The forward picked up the ball deep in his own half following a Chelsea corner, ran past the challenge of the covering Fernandez, around Kepa Arrizabalaga and tapped into an empty net.
Chelsea came agonisingly close to levelling when Koulibaly sent an effort at goal and the ball rolled dangerously along the goalline where Emre Can slid in to make a brilliant clearance.
Fernandez had the final chance for the Blues, but his powerful stoppage-time strike was blocked by Kobel to seal victory for the hosts.