First half goals from Stefan Kiessling, with some help from blundering Benfica keeper Julio Cesar, and Son Heung-min settled the hosts' nerves and put them on track for their first win in the competition with a dominant performance.
Eduardo Salvio briefly pulled one back for the struggling Portuguese in the 62nd minute before a Hakan Calhanoglu spot kick settled matters only a minute later.
Leverkusen moved up to three points, one behind Zenit St Petersburg and Monaco, who drew 1-1 earlier on Wednesday. Benfica, who were exceedingly weak with not a single shot on or off target for more than an hour, are bottom of the group without a point.
The hosts set a fierce pace early on with South Korean Son almost scoring after four minutes and only being denied by a fine save from Brazil keeper Julio Cesar.
Lars Bender then hit the post with a deflected shot from inside the box as the hosts continued to press for a quick goal to put them in control.
Cesar, a replacement for suspended Artur, gifted the Germans the lead when, after blocking a shot by Son, he spilled the ball into the path of Kiessling, who tapped in.
Son then scored one of his own in the 34th minute with Karim Bellarabi cutting into the box and finding the Korean, who rifled into the top corner from 12 metres.
Hakan Calhanoglu hit the post from a metre out early in the second half with Leverkusen looking to kill the game off early.
Argentine Salvio gave the visitors a glimmer of hope when he threaded a shot past keeper Bernd Leno with their only shot on goal in the entire game.
Kiessling was then brought down by Jardel for a penalty and Calhanoglu made amends for his earlier miss, sending Cesar the wrong way.
(Reporting by Karolos Grohmann)
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