Third tier Lotte scored twice to knock out 1860, while Schalke turned on the style away to Sandhausen. Borussia Dortmund beat Hertha Berlin on penalties and Eintracht Frankfurt edged out Hannover in a dramatic finale.
Lotte 2-0 1860 Munich
(Lindner 28, Freiberger 58')
Third tier Lotte scored a goal in each half as they eased to a comfortable win over second tier 1860.
Jaroslaw Lindner opened the scoring from a tight angle, lashing a venomous shot into the roof of the net after 1860 keeper Stefan Ortega parried the ball to his right.
1860 battled for a route back into the game but their hopes of drawing level were extinguished when Kevin Freiberger beat the offside trap and poked the ball around Ortega and stroked into the empty net.
The visitors' misery was complete when Ribamar was sent off in the last minute for a mindless foul.
Hannover 96 1-2 Eintracht Frankfurt
(Harnik 57' - Tawatha 62', Seferovic 66')
Hannover's Salif Sane missed a 96th minute penalty as Frankfurt reached the last eight in a dramatic finale.
Martin Harnik seized on some uncertain Frankfurt defending to open the scoring, poking the ball under Lucas Hradecky.
But Frankfurt responded five minutes later through Taleb Tawatha's header from Timothy Chandler's cross. Only four minutes after that frankfurt had the lead, with Seferovic pouncing on a poor defensive header and slotting the ball home.
Hannover had the chance to force extra time when they were awarded a penalty deep into injury time, but Sane's poor penalty was saved by Hradecky.
Borussia Dortmund 1-1 Hertha Berlin (Dortmund won 3-2 on pens)
(Reus 47' - Kalou 27')
Salomon Kalou missed the crucial penalty as Borussia Dortmund edged out Hertha Berlin on penalties.
Kalou had put Hertha ahead with a fine volley in front of the Südtribüne, stretching to deftly direct Niklas Stark's cross into the net.
Hertha took their lead into the break, but Thomas Tuchel's side responded two minutes after the restart, with Marco Reus steering the ball in after Ousmane Dembele's initial effort had come back off the post.
With the game in the final minutes of extra time, Dortmund's Sokratis was sent off for dissent just ahead of the shootout, which was clinched when Kalou sent his penalty high over the bar.
Sandhausen 1-4 Schalke
(Wooten 65' - Schöpf 38', Caligiuri 43', Naldo 45', Konoplyanka 71')
Schalke turned on the style as they swept second tier Sandhausen aside.
Alessandro Schöpf's scrappy strike from close range opened the floodgates, with Daniel Caligiuri doubling Schalke's lead with a well struck shot and Naldo making it three with a header in first half stoppage time.
Sandhausen gave themselves a lifeline midway through the second half through Andrew Wooten, but Yevheniy Konoplyanka completed the rout with Schalke's fourth.
Wednesday's action as it happened: