Two goals from the league’s top scorer Stefan Kiessling and one from Andre Schurrle earned the side coached by Sami Hyypia and Sascha Lewandowski all three points, guaranteeing them second spot going into 2013.
Hamburg, who went on a trip to South America following their 2-0 win over Hoffenheim last weekend, showed more than a few signs of tiredness as they were unable to match their high-flying hosts.
Leverkusen had the chance to take the lead in the third minute when Schurrle hit the left post with only Rene Adler to beat.
It was an indication of things to come for Adler, who was in for a very busy 90 minutes against his former club.
Simon Rolfes tested him with a shot from distance before Kiessling found a way through in the 26th minute.
Schurrle’s cross was touched on delicately but decisively by Gonzalo Castro to find the Bundesliga’s top scorer for 2012, who netted his 10th of the current campaign and his 24th of the calendar year.
Leverkusen’s celebrations were almost cut short when Artjoms Rudnevs headed against the post at the other end, but instead they were amplified when Schurrle made it two in the 36th minute.
It was a fast move involving Jens Hegeler and Kiessling, with Schurrle keeping up the pace to beat Michael Mancienne and then touch the ball past Adler off the inside of the post.
Leverkusen struck the woodwork once again in the 65th minute with Castro’s shot crashing against the crossbar.
The home side were in buoyant mood and they added a third a minute later when Kiessling lifted the ball over Adler from Bernd Leno’s long punt forwards.