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'onnz 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.
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, as familiar faces return in Supergirl's 100th episode.
Lex tasks Supergirl with protecting Andrea from an anti-tech extremist, but his nefarious purpose goes beyond merely keeping Andrea alive. With Alex's help, Lena moves forward with Non Nocere.
Nia's roommate is attacked by a man targeting Dreamer because he doesn't like that Dreamer is transgender and wants her to quit being a superhero. Determined to protect her community from additional harm, Dreamer refuses to give into his threats and puts herself in the line of fire to stop him. Alex, J'onn and Kelly attempt to rescue a man stuck inside a virtual reality escape room.
Alex uses a pair of Obsidian contact lenses to visit a virtual National City where she takes on a whole new persona. Kelly helps William investigate Lex. Kara deals with difficult news.
Lex proceeds to lay an intricate plan to bring Lena closer to him, defeat Leviathan's latest attack, and pit Supergirl and team against Leviathan. It is also revealed how Lex came into power after Crisis.
Supergirl and the team go head to head against Rama Khan and Leviathan. Meanwhile, Lena and Lex must join forces when Project Non Nocere fails, leaving the two siblings in serious danger.
Supergirl realizes that in order to stop Lex and Leviathan she must work with the one person she never thought she'd trust again - Lena. Nia keeps dreaming about Brainy but struggles with what the dreams are trying to tell her. Meanwhile, Brainy realizes there is only one way to stop Lex.