Kiessling had been at the centre of controversy with a 'ghost goal' in his side's Bundesliga win over Hoffenheim last week, but there was no doubt about his strikes on Wednesday as he headed the Germans in front midway through the first half, before Simon Rolfes slotted home from the spot just after the break.
Sidney Sam added a third with a well-taken finish, before Kiessling poked home his second of the night with 18 minutes left to confirm the win.
The result extends Leverkusen's unbeaten run at home in the Champions League group stages to eight games, and leaves them just a point behind Group A leaders Manchester United.
Leverkusen coach Sami Hyypia made four changes to the side that beat Hoffenheim, with Emir Spahic, Giulio Donati, Emre Can and Son Heung-Min all handed starts. Lars Bender missed out with a thigh injury.
Much had been made of Shakhtar's attacking threat, but the visitors struggled to find to find any sort of rhythm during the early exchanges, although the hosts breathed a sigh of relief when Yaroslav Rakitsky sent an early free-kick just wide of the post.
Leverkusen continued to have the upper hand in the centre of the park, and they were rewarded for their efforts after 23 minutes when Kiessling rose brilliantly to meet Donati's whipped cross and head his side into the lead.
Shakhtar substitute Bernard should have found the net 10 minutes later, but he could not connect with Douglas Costa's low cross.
The hosts could have had a fifth late on, with both Can and Sam missing good opportunities, on what was otherwise a fantastic night for Hyypia's men.
