Stuttgart, putting aside their domestic worries where they are stuck in the bottom two of the Bundesliga and four points adrift of safety, looked on course for a possible upset when they took the lead in the 21st minute through a fine goal from Martin Harnik.
However, Benfica, who had won 10 successive league and cup games prior to this match, stormed back in the second half and Oscar Cardozo drew the hosts level in the 70th minute before Franco Jara added a second nine minutes from time.
Both sides went close to scoring in the closing stages, but the match finished 2-1 to leave the tie is evenly poised for the second leg.
Stuttgart started well and Shinji Okazaki brought a diving save out of Roberto Jimenez early on before the German side took the lead through Harnik, who raced onto a lofted through-ball from Tamas Hajnal, took one touch to control before lifting a perfect lob over the stranded Roberto.
Benfica felt they should have got a penalty just before the break when Fabio Coentrao appeared to be brought down by Stuttgart goalkeeper Sven Ulreich, but all Coentrao got was a yellow card for diving.
Aside from that incident, Benfica created little to concern Ulreich before the break - but it was a completely different story in the second half.
Ulreich was called on to produce vital saves from Coentrao, Pablo Aimar (twice) and Nicolas Gaitan in quick succession as Benfica started to turn the screw.
It was no real surprise therefore when the home side got back on level terms midway through the second half.
A Gaitan cross into the box ended up falling perfectly for Cordozo, who fired a first-time shot past Ulreich from the just inside the area.
Benfica then got their noses in front 11 minutes later through Jara.
Jara's 25-yard shot took a significant deflection that saw it loop over Ulreich, and although the visiting goalkeeper managed to tip the ball onto the underside of the crossbar, it bounced down over the line before Cardozo smashed the ball in just to be sure.
That was no more than Benfica deserved, but they almost lost their advantage moments later when Stuttgart hit the foot of the post through Christian Trasch's 25-yard free-kick.
Having survived that scare, Benfica laid siege to the Stuttgart goal in the final minutes and Alan Kardec, Felipe Menezes, Javi Garcia (twice) and Cardozo all went close without being able to get the ball into the net.
Benfica 2-1 VfB Stuttgart: Match Report - view commentary, squad, and statictics of the game as it happened.