Goals from Jeremie Frimpong and Amine Adli provided Bundesliga leaders Leverkusen with a comfortable advantage within the first 20 minutes.
Florian Wirtz then scored twice, once before halftime and once after, including one from the penalty spot, completing a dominant performance.
Leverkusen’s lone German Cup victory in 1993 marked the club’s last major trophy.
Kaiserslautern defeated third-tier Saarbrucken 2-0 in their semi-final on Tuesday.
Under Xabi Alonso’s leadership, Leverkusen remains undefeated this season and contends for three trophies.
They currently sit 13 points clear at the summit of the Bundesliga as they pursue their first-ever German league title, while also preparing to face West Ham in the Europa League quarter-finals later this month.
Leverkusen last appeared in the DFB-Pokal final in 2020, where they suffered a 4-2 defeat to Bayern Munich.
Dusseldorf, currently third in the second tier, had aspirations of reaching the cup final for the first time since 1980.
The season’s showcase event is scheduled for May 25th at the Olympiastadion in Berlin.