When an alien attacks National City, Supergirl and the DEO learn the alien is a Phorian, an otherwise peaceful race with telekinetic powers. Guardian gets a lead on the Phorian's address but instead of finding the culprit, he finds a very scared boy named Marcus. Marcus will only trust James so it is up to Guardian to stop the attacks on the city. Rhea's plan escalates.

Someone tries to kill Morgan Edge and he barely survives. He accuses Lena of being behind the attempt and vows to destroy her. When Lena fears her hatred for Morgan will take her to the Luthor dark side, Kara steps in to help her friend. Meanwhile, after Sam realizes she’s losing time, she confides in Alex who decides to run some medical tests to see if she can find out what’s going on with her new friend.

When Reign starts hunting Ruby, Supergirl and Alex work together to keep her safe. Supergirl and J'onn look to Sam’s mother for advice on how to stop Reign and come away with some shocking news.

Diving back into reporting, Kara welcomes a new cub reporter to CatCo. Meanwhile, James and Lena argue about James’ impending indictment for acting as the vigilante Guardian, while Alex and Brainy struggle to get in sync at the DEO. Supergirl is called into action when remnants of the anti-alien terrorist organization Cadmus try to assassinate pro-alien leaders, but their endgame turns out to be much more sinister than she expected. J’onn relishes his peaceful new life, but an outing with an old friend causes him concern.

With his P.I. shingle newly hung outside his office, J'onn welcomes new clients. Trying to take her mind off what happened at the DEO, Kara decides to team up with J'onn on his latest assignment, which unfortunately ends up tying directly into Alex's current investigation that involves the villain Menagerie. Meanwhile, Lena shares some news with James, but his reaction isn't what she expected. Nia invites Brainy to her Valentine's Day party.

Lex Luthor descends upon Washington, DC and summons Lena and Lillian Luthor to the White House. Supergirl realizes she has one last chance to stop Lex and turns to the power of the press to help her.

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 S05E01.

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 Brainiac lays close to death after trying to stop Lex, Supergirl and team soar in to save him, engaging in an epic battle with Gamemnae. After beating Leviathan, Supergirl turns her attention to Lex who has used the Obsidian platform to brainwash half the world to love him and follow him at all costs, no matter what horrible things he does. Knowing how dangerous this makes her brother, Lena enlists the entire team – Alex, J’onn , Dreamer, Kelly and Brainiac – to help, but Supergirl realizes that the only way to truly stop Lex is to sacrifice herself.

Supergirl continues to fight Nyxly for the remaining totems but after Nyxly kidnaps William, Supergirl realizes she needs to take a more proactive stance to keep National City safe. Meanwhile, Alex faces the biggest challenge of her life.

Supergirl is joined by familiar faces from the past to help her stop Lex and Nyxly for good. Meanwhile, Alex and Kelly prepare to walk down the aisle.