This was Jesse Marsch's first season as coach, succeeding Julian Nagelsmann before being sacked mid-season.

[1] Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

The draw for the knockout round play-offs was held on 13 December 2021.

[28] After being drawn against Russian side Spartak Moscow, Leipzig received a bye to the next round following Spartak's expulsion by UEFA and FIFA due to the Russian invasion of Ukraine.