Werder Bremen had a player sent off as they crashed out of the German Cup in a first-round 2-1 defeat at third-division Sportfreunde Lotte on Sunday.
Bayer Leverkusen struggled to beat fifth-tier Hauenstein 2-1, while fellow Bundesliga sides Mainz, Eintracht Frankfurt, Hertha Berlin and Ingolstadt survived penalty shoot-outs against lower-division teams.
Elsewhere there were comfortable wins for top-flight teams Hoffenheim and Darmstadt against amateur opponents.
Andrej Kramaric scored a hat-trick as Hoffenheim enjoyed a 6-0 run-out at fourth-tier Egestorf/Langreder, while Darmstadt cruised to a 7-0 win at fifth-tier Bremer SV with Antonio-Mirko Colak helping himself to three goals.
Werder's Fin Bartels was shown a red card eight minutes from time as the six-time cup winners went out to Lotte in another first-round debacle for the northern German club.
Matthias Rahn gave Lotte an eighth-minute lead, and Andre Dej put the home side ahead nine minutes after the break following a headed equalizer from Werder's Zlatko Junuzovic.
Bremen have made a habit of struggling against lower division sides in the first round in recent seasons.
They went out in the first round to third-division opponents three years in a row between 2011 and 2013. The following season they scraped though against fourth-tier opponents and last year beat then-third-division Kickers Wuerzburg in extra-time before reaching the semi-finals.
Coach Viktor Skripnik said: "That was a deserved win for Lotte. We imagined things would be completely different and are really disappointed.
"Last season we surprisingly reached the semi-finals; this year we have surprisingly gone out in the first round. That's football."
Bremen join RB Leipzig as Bundesliga first-round casualties after the newly-promoted top-flight side went out on penalties Saturday to Dynamo Dresden.
Leverkusen scraped through at Hauenstein, with goals from Javier Hernandez in the 39th minute and Karim Bellarabi in the 68th before the minnows hit back with an Andelo Srzentic header nine minutes from time.
Mainz conceded two late goals in a 3-3 draw after 90 minutes at fourth-tier Unterhaching and after a goalless extra period the Bundesliga club won the penalty shoot-out 4-2.
Third-division Magdeburg and Frankfurt finished 1-1 after full-time and extra-time in a game interrupted by crowd trouble in the second half. Frankfurt then got the better of the shoot-out, with Guillermo Varela, on loan from Manchester United, scoring the decisive spot-kick in a 4-3 win on the penalties.
A Mitchell Weiser header seven minutes before the end took Hertha Berlin 1-1 into extra-time at third-division leaders Jahn Regensburg, and after no further goals Hertha won the penalty shoot-out 5-3.
Ingolstadt were goalless after extra-time at second-division Erzgebirge Aue before winning 8-7 on penalties.
Elswehere, second division Greuther Fuerth ran out 4-1 winners at fourth-tier Eintracht Norderstedt, second-division Union Berlin won 2-1 after extra-time at third-division Duisburg, fourth-tier Astoria Walldorf upset second-division Bochum 4-3 after extra-time, and second-division Heidenheim won 2-1 at fourth-tier Wattenscheid.
The first round concludes Monday with four more games including Borussia Dortmund at fourth-tier side Eintracht Trier.