After a 1-0 win in Portugal last week, Karim Bellarabi scored his second in as many games against the capital club to give Leverkusen some breathing space.
However, Joao Mario responded quickly for Sporting. The tie could have went either way but another Bellarabi strike and Hakan Calhanoglu's late goal secured the win.
Bellarabi breakthrough, Joao Mario makes it all square
Leverkusen began brightest and forced Rui Patricio into a set of early saves. Bellarabi, Calhanoglu, Stefan Kießling and Wendell all went close, either being denied by the experienced stopper of firing off target. It was a dominant start, but the crucial first goal was yet to be scored.
Finally, after all their good play, Leverkusen made the breakthrough. A wonderful pass from Calhanoglu found the run of Javier Hernandez, who quickly fed the ball into Bellarabi. From a tight angle, the winger finished with aplomb to hand the hosts a sizeable advantage.
Jorge Jesus then let Carlos Mané and Joao Mario come forward at will, which pushed the Leverkusen defence to breaking point. The former missed an excellent chance and only a minute later was denied by a spectacular Bernd Leno stop. He was unable to keep out the rebound, however, as Joao Mario finished from close range.
Two second half strikes see Leverkusen through
The start of the second period was nothing like the first, despite the introduction of Admir Mehmedi for Julian Brandt by Roger Schmidt. Kießling was then forced off with injury, while Wendell was perhaps lucky not to see red, or even a card, for a supposed elbow on Bruno Cesar.
Moments after Kießling came off, Bellarabi struck again. His third goal in the tie was by far the best, as he collected a pass from André Ramalho on the edge of the area before firing the ball into the top right hand corner. The Sporting defence were motionless, Bellarabi joyous.
Despite the visitors pushing on to try and force a way back into the game, it was Leverkusen who would grab the game's final goal. A fantastic ball forward from Jonathan Tah picked out Calhanoglu, who produced a fine finish from 18 yards to condemn Sporting to their 11th defeat in 12 games in Germany. Leverkusen now await their opponent in Friday's draw.