First-half goals from Marcus Berg and Maximilian Beister gave the visitors the upper hand but Koen van der Biezen and Selcuk Alibaz scored equalisers.
And the third-tier outfit stunned their illustrious opponents with two goals in the final 12 minutes from Martin Stoll and Elia Soriano to secure their spot in the second round.
Regionalliga side Havelse sprung a major surprise by knocking Bundesliga side Nuremberg out with a 3-2 extra-time victory.
Despite Alexander Esswein's early opener, Nuremberg required Robert Mak's 80th-minute equaliser to see them into extra time.
But Marc Vucinovic struck early in the second extra period to add to Christoph Beismann and Patrick Posipal's goals in normal time and see the Pelikans through.
Werder Bremen crashed out after extra time to Preussen Munster, from the same level of the game, after Matthew Taylor's hat-trick.
The American equalised twice to ensure extra time after first Eljero Elia and then Niclas Fullkrug had given Werder the lead.
And Dima Nazarov put the hosts 3-2 ahead before Werder had Sokratis Papastathopoulos sent off and Taylor grabbed his third late on.
Eintracht Frankfurt had Kevin Trapp sent off inside 20 minutes as they were hammered 3-0 by second-tier Erzgebirge Aue.
Thomas Paulus scored from the resulting penalty and Jakub Sylvestr's double ensured there was no way back for the Bundesliga side, despite the dismissal of Aue's Oliver Schroder at 2-0.
Regionalliga side Wormatia Worms beat Hertha Berlin of the 2.Bundesliga 2-1.
Tim Bauer set the minnows on their way with a third-minute penalty and, despite Sandro Wagner's equaliser, Romas Dressler's winner sent the Worms into the next round.
Sergio Pinto and Jan Schlaudraff scored twice apiece as Hannover cruised past Nottingen 6-1 and Julian Draxler and Ciprian Marica did likewise in Schalke's 5-0 win over Saarbrucken, while 1860 Munich enjoyed a 6-0 success against Hennef with six different goalscorers.
Aalen beat 2.Bundesliga rivals Ingolstadt 3-0 and Paderborn were beaten 3-1 by third-division Arminia Bielefeld after late goals from Patrick Schonfeld and Thomas Hubener.
Kaiserslautern are through to the second round after a 3-1 victory at 2. Bundesliga rivals Hansa Rostock.
Albert Bunkaju gave the visitors a 49th minute lead before Hendrick Zuck doubled their advantage seven minutes later.
Johan Platt gave the home side hope with a goal 14 minutes from time, but Konstantinos Fortounis secured Kaiserslautern's progression in added time.
Fortuna Dusseldorf will join them after Stefan Reisinger netted a 76th minute winner at SV Wacker Burghausen.
Mainz eased to a 4-0 win over Oberliga side Rossbach Verscheid. Adam Szalai scored twice before the break with Julian Baumgartliner adding to the tally three minutes after the interval.
Maxim Choupo-Moting completed the scoring after 62 minutes to seal their progression.