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.
Kara is surprised to find that CatCo has a new owner who has brought in a star reporter. New couples emerge and explore their budding relationships while J’onn J’onzz receives an unexpected visitor.
Supergirl, Alex, and Brainiac thwart an alien attack while William investigates Kara. J'onn J'onzz and Kelly use Obsidian tech to solve a problem.
Kara attempts to mend her relationship with Lena. J’onn J’onzz takes a deep dive into his memories while Kelly tries to help an old friend.
Kara's investigation into William Dey's "criminal" activities results in the shocking revelation he is not who she thinks. Meanwhile, the conflict between Malefic and J'onn J'onzz reaches a boiling point.
On the eve of the worldwide launch of Andrea Rojas's VR contact lenses, Kara and William team up on an investigation that exposes a terrorist plot. Kelly and Alex celebrate an anniversary, but Alex's safety is in jeopardy.
While a new villain is under arrest at the DEO, Supergirl uses him to try and understand who is responsible for the recent attacks. Meanwhile, Andrea and Lena think back on their tumultuous past.
Supergirl finally learns the truth about Lena while tangling with Leviathan. J'onn J'onn makes a discovery about his brother's whereabouts.
Supergirl's struggle against Leviathan reaches a boiling point as she faces off against Rama Khan. Meanwhile, as Lena and Hope work to launch Project Non Nocere, Hope proves to be an invaluable asset to Lena.
The Monitor sends Harbinger to gather the worlds’ greatest heroes - Supergirl, The Flash, Green Arrow, Batwoman, White Canary, The Atom and Superman - in preparation for the impending Crisis. With their worlds in imminent danger, the superheroes suit up for battle while J’onn and Alex recruit Lena to help them find a way to save the people of Earth-38. This crossover continues on Batwoman S1E09, The Flash S6E09, Arrow S8E08, and Legends of Tomorrow's special episode.
The subsequent complications from the Crisis leave Supergirl to face a chaotic threat.
As Supergirl tries to thwart a Toyman copycat, Winn Schott returns from the future.
Supergirl helps Winn face his greatest fear. After Alex sets out to find evidence against Lex, Brainy must decide between helping his friend or continuing to secretly work for Lex.
Mxyzptlk returns with a proposition for Kara – what if she could go back in time and tell Lena her secret before Lex did, would things turn out different? Looking back over key moments throughout the series, Kara must decide if she wants to change history to become friends with Lena again.
Lex tasks Supergirl with protecting Andrea from an anti-tech extremist, but his nefarious purpose goes beyond merely keeping Andrea alive. Meanwhile, Lena moves forward with Non Nocere, with Lex’s help.