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.

When Kara’s attempts to help National City don't go according to plan, she must put aside the doubts that she -- and the city's media -- has about her abilities in order to capture an escapee from the Kryptonian prison, Fort Rozz. Also, Cat pressures James to use his connection to Superman to get her an interview with Supergirl.

Supergirl’s powers are tested when Reactron, one of Superman’s formidable enemies, arrives in National City and targets the young hero. Also, Cat plans to run an exposé on Supergirl.

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.

Kara’s two identities are stretched thin when Supergirl must protect National City from a series of bombings and Kara is tasked with babysitting Cat’s son, Carter. Also, James is conflicted when his ex-girlfriend Lucy Lane seeks to rekindle their relationship.

Personal and professional stress get the better of Kara when she goes too far during a training exercise against Red Tornado, a military cyborg commissioned by Lucy Lane’s father, General Sam Lane. Also, Cat’s tough exterior is shaken by a visit from her judgmental mother, Katherine, and Alex enlists Winn to look into her father’s mysterious death.

Kara and her friends must rely on their inner strength and courage when an earthquake strikes National City. Also, Alex’s mistrust of Hank reaches a breaking point when the earthquake traps them in the DEO with Jemm, a powerful alien escapee.

Kara goes toe-to-toe with Astra when her aunt challenges Kara’s beliefs about her mother. Also, Cat is threatened with being removed as the CEO of CatCo after a hacker exposes her private and damaging emails.

With Astra in captivity at the DEO, her husband, Non, captures Hank, leading to a tense standoff between the two sides. Also, Kara continues to refute Cat's allegations that she is Supergirl.

Kara does her best to support Winn when his father, the supervillain Toyman, breaks out of prison and seeks out his son for unknown reasons. Also, Cat offers Lucy a job at CatCo and Alex asks Hank to use his powers to help uncover Maxwell Lord's plan.

Kara must help Hank face his painful past when a White Martian, a member of the alien race that wiped out his people, kidnaps Senator Miranda Crane, an anti-alien politician. Also, Cat's estranged son, Adam, arrives in National City.

Kara faces off against her mirror image when Bizarro, a twisted version of Supergirl, sets out to destroy her. Also, Kara grows closer with Cat’s son, Adam.

Kara’s friends must find a way to save her life when a parasitic alien attaches itself to her and traps her in a dream world where her family is alive and her home planet was never destroyed. Also, Alex, Hank and the DEO must fend off a Kryptonian attack while Kara is out of commission.

Supergirl does battle with the deadly Master Jailer, who is hunting and executing escaped Fort Rozz prisoners. Also, Cat hires a second assistant, Siobhan Smythe, who immediately tries to one-up Kara, and Kara and James disagree over the DEO's methods.

Kara travels to Superman’s Fortress of Solitude in hopes of learning how to defeat Indigo, a dangerous being who can transport via the Internet and who has a connection to Kara’s past. Also, James’s relationship with Lucy reaches a crossroads.

Kara turns on her friends and the citizens of National City after being exposed to Red Kryptonite makes her malicious and dangerous. Also, Cat appears on THE TALK to discuss 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.

Kara must find a way to free her friends when Non and Indigo use mind control to turn National City’s citizens into their own army.

Supergirl is forced to do battle with an unexpected foe and must risk everything – including her life – to prevent Non and Indigo from destroying every person on the planet.