Twenty-four-year-old Kara Zor-El, who was taken in by the Danvers family when she was 13 after being sent away from Krypton, must learn to embrace her powers after previously hiding them. The Danvers teach her to be careful with her powers, until she has to reveal them during an unexpected disaster, setting her on her journey of heroism.
| Actor | Role |
|---|---|
 Melissa BenoistKara Danvers / Supergirl / Kara Zor-El | Kara Danvers / Supergirl / Kara Zor-El |
 Chyler LeighAlex Danvers / Sentinel | Alex Danvers / Sentinel |
 David HarewoodJ'onn J'onzz / Martian Manhunter | J'onn J'onzz / Martian Manhunter |
 Katie McGrathLena Luthor | Lena Luthor |
 Jesse RathQuerl 'Brainy' Dox / Brainiac-5 | Querl 'Brainy' Dox / Brainiac-5 |
 Nicole MainesNia Nal / Dreamer | Nia Nal / Dreamer |
 Azie TesfaiKelly Olsen / Guardian | Kelly Olsen / Guardian |
 Julie GonzaloAndrea Rojas / Acrata | Andrea Rojas / Acrata |
 Staz NairWilliam Dey | William Dey |
 Peta SergeantNyxlygsptlnz / 'Nyxly' | Nyxlygsptlnz / 'Nyxly' |