I seriens premiereafsnit vælger Supermans kusine, Kara Zor-El - efter i 12 år at have skjult sine kræfter på Jorden - langt om længe at anvende sine overmenneskelige evner og blive den helt, det er hendes skæbne at blive.

Kara's Thanksgiving may be ruined when she suspects her foster mother, Dr. Danvers, who is coming to town, disapproves of her new role as a superhero. Also, when an accident transforms a volatile CatCo employee into the villainous Livewire, she targets Cat and Supergirl.

J'onn J'onzz reveals the details of meeting Kara and Alex's father, Dr. Jeremiah Danvers, and assuming Hank Henshaw's identity. Also, Kara debates trusting someone new with her secret identity and Siobhan plots against Kara.

While Guardian tries to clear his name after being accused of a murder committed by another vigilante, Supergirl heads out on a solo mission to rescue Mon-El who has been captured by Cadmus. While fighting to free Mon-El, Supergirl comes face to face with Cyborg Superman.

When Jeremiah Danvers is rescued from Cadmus, Alex and Kara are thrilled to have their father back. The Danvers arrange a family dinner to celebrate but things go awry when a suspicious Mon-El starts to question Jeremiah about his sudden return.

As Alex searches for Jeremiah and Kara investigates a series of alien kidnappings, the sisters realize they must break the rules to foil a new Cadmus plot. In an effort to get Snapper Carr to run a story that would help her stop Cadmus, Kara agrees to set up an interview between Snapper and Supergirl.