| October 16, 2021 | ||
| Borussia Dortmund | 15:30 | Mainz |
| Greuther Fürth | 15:30 | VFL Bochum |
| Eintracht Frankfurt | 15:30 | Hertha Berlin |
| SC Freiburg | 15:30 | RB Leipzig |
| Union Berlin | 15:30 | Wolfsburg |
| Borussia Mönchengladbach | 18:30 | Stuttgart |
| October 17, 2021 | ||
| Bayer 04 Leverkusen | 15:30 | Bayern Munich |
| Augsburg 1907 | 17:30 | Arminia Bielefeld |
| October 22, 2021 | ||
| Mainz | 20:30 | Augsburg 1907 |
| October 23, 2021 | ||
| Bayern Munich | 15:30 | TSG 1899 Hoffenheim |
| RB Leipzig | 15:30 | Greuther Fürth |
| Wolfsburg | 15:30 | SC Freiburg |
| Arminia Bielefeld | 15:30 | Borussia Dortmund |
| Hertha Berlin | 18:30 | Borussia Mönchengladbach |
| October 24, 2021 | ||
| FC Cologne | 15:30 | Bayer 04 Leverkusen |
| Stuttgart | 17:30 | Union Berlin |
| VFL Bochum | 19:30 | Eintracht Frankfurt |
| October 29, 2021 | ||
| TSG 1899 Hoffenheim | 20:30 | Hertha Berlin |
