Borussia Moenchengladbach were upset 2-1 at second division leaders Darmstadt 98 after a 79th-minute winner from Germany youth international Aaron Seydel in the German Cup second round.
Gladbach's exit was the biggest shock on Tuesday with substitute Seydel scoring four minutes after coming on.
Darmstadt forward Phillip Tietz had put the hosts in front in the 23rd minute before Gladbach's Luca Netz equalised five minutes after the restart from an Alassane Plea pass.
Darmstadt bounced back when the visiting defence was unable to stop striker Seydel who sealed the victory with a precise low shot from the corner of the six-yard box.
Hoffenheim cruised to a 5-1 win over struggling Schalke 04 in an all-Bundesliga battle with two goals from striker Mu'nas Dabbur to move into the third round.
Hoffenheim, who sit fourth in the Bundesliga six points behind leaders Union Berlin, enjoyed a stellar display against relegation-threatened Schalke, who have so far managed one Bundesliga win and only six points from 10 games.
Dabbur put the hosts ahead after five minutes from close range while midfielder Angelino doubled their advantage with a low shot from outside the box in the 16th.
Hoffenheim made it 3-0 through another Dabbur strike just before halftime as he fired the ball from a very tight angle into the far top corner.
Ozan Kabak and Pavel Kaderabek were also on target for the hosts while Schalke midfielder Dominick Drexler grabbed a consolation goal in the 69th minute.
Earlier on Tuesday, RB Leipzig striker Yussuf Poulsen struck twice to guide the holders to a 4-0 home victory over second-tier side Hamburg SV.
The Denmark international found the net against last year's semifinalists in the 33rd and 36th minutes for his first goals since April. Defender Mohamed Simakan and midfielder Benjamin Henrichs wrapped up the victory in the second half.
Eintracht Frankfurt needed just 11 minutes to open the scoring in their 2-0 win at fifth-tier club Stuttgarter Kickers.
Forward Randal Kolo Muani, who in September received his first call-up by France, lobbed goalkeeper Ramon Castelluci to hand Eintracht the lead and defender Hrvoje Smolcic put them further in front with a header in the 18th minute.
Mainz 05 eased past fourth-tier VfB Luebeck 3-0 while VfL Wolfsburg edged second-tier Eintracht Braunschweig 2-1 away.
Bayern Munich travel to Augsburg on Wednesday, while Borussia Dortmund face Hanover 96.