Leverkusen, who sit fourth in the Bundesliga, looked set for a routine victory over Regionalliga side Magdeburg when Hakan Calhanoglu put them in front with a free-kick after just three minutes at the MDCC-Arena on Wednesday but the home team had other ideas.
The fourth-tier side drew level courtesy of former Leverkusen midfielder Christoph Siefkes' strike 28 minutes in and the hosts must have fancied their chances of a major upset when Leverkusen striker Son Heung-Min was shown a straight red card in the 78th minute.
Magdeburg, conquerors of Bundesliga outfit Augsburg in the first round, then went 2-1 up with nine minutes of extra-time remaining when Niklas Brandt found the back of the net but Kyriakos Papadopoulos headed home with five minutes remaining to force a shootout.
A shock looked to be on the cards again when Emir Spahic missed Leverkusen's first spot-kick and after Stefan Kiessling also failed to convert from 12 yards, Magdeburg needed to score just one of their last two penalties.
However, Brandt and Nicolas Hebisch both failed to hold their nerve and after the Bundesliga side turned it around to lead 5-4, Lars Fuchs was denied by Leverkusen goalkeeper Bernd Leno to leave the hosts wondering what might have been.
Holders Bayern Munich had no such trouble as they eased to a comprehensive 3-1 victory over Hamburg.
The Bundesliga champions were never under any threat at the Imtech Arena as goals from Robert Lewandowski, David Alaba and Franck Ribery, making his first start of the season, inflicted more misery on Josef Zinnbauer's side.
Home goalkeeper Jaroslav Drobny had to be alert to deny Ribery a spectacular second with 17 minutes remaining and although Pierre-Michel Lasogga pulled a goal back five minutes from time, the damage had already been done.
Hamburg could find themselves in hot water after a fan ran onto the pitch and swung his scarf in Ribery's face in stoppage time.
Freiburg are without a win in the Bundesliga but did not resemble a struggling side as Admir Mehmedi inspired their 5-2 hammering of Bundesliga 2 outfit 1860 Munchen.
Switzerland international Mehmedi helped himself to a hat-trick, while Sebastian Freis and Jonathan Schmid were also on target after Valdet Rama had put the home side in front.
Borussia Monchengladbach's impressive start to the season continued as they won 2-1 in an all-Bundesliga tie at Eintracht Frankfurt, with Thorgan Hazard and Ibrahima Traore doing the damage.
Roberto Firmino scored twice as Hoffenheim cruised to a 5-1 home victory over FSV Frankfurt, while Luiz Gustavo also claimed a double in Wolfsburg's 4-1 win against Heidenheim at the Volkswagen Arena.
RB Leipzig ran out 3-1 winners after extra-time against fellow side Bundesliga 2 club Erzgebirge Aue and Eintracht Braunschweig avoided an upset by winning 1-0 at Regionalliga outfit Wurzburger Kickers.
