In addition to the domestic league, Real Betis participated in this season's editions of the Copa del Rey and the UEFA Europa League.

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.

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

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