The pacey penetrations of Petersburg men down the flanks were the determining factor behind the Russian team's stunning victory at the BayArena.
The impressive win means that Petersburg have gained a shocking advantage in the first-leg of the competition's quarter final.
Andre Arshavin stunned the home crowd after 19 minutes when he muscled his way into Leverkusen area before firing into the roof of the net from a tight angle.
Stefan Kiessling drew Leverkusen level in the 33rd minute with a close-range finish but his side were completely outplayed afterwards.
Pavel Pogrebnyak restored Petersburg's lead seven minutes after restart after being set-up by Arshavin's cross.
Aleksandr Anyukov made it 3-1 in the 61st after his weak shot went past Leverkusen keeper Rene Adler before Igor Denisov completed the rout three minutes later.