As Lex Luthor forces half the people of the Earth to be his followers by brainwashing them, he tries to eliminate the rest of mankind. Meanwhile, Kara Danvers tries to destroy Lex's satellites, but he manages to defeat her and her friends, after which he gets arrested.
Supergirl ends up in the Phantom Zone, where she is saved from the Phantoms by her father, Zor-El; meanwhile, Alex Danvers and J'onn attempt to rescue her. On the other hand, Lex gets tried but is eventually acquitted.
After a confrontation with a Phantom, Zor-El gets captured, while Kara suffers an injury, but Nyxly cures her, and they manage to save Zor-El. Elsewhere, Lena clashes with Lex over the management of Luthor Corp and its funds.
As Kara, Nyxly, and Zor-El try to find their way back from the Phantom Zone, Lena invents a device to find Kara there; however, Lena and Alex fail to agree on a course of action.
In an attempt to get Kara's DNA to be able to track her in the Phantom Zone, Brainiac-5 and Nia embark on an action-packed adventure, traveling back in time to 2009 Midvale.
Cat Grant unintentionally puts Supergirl in jeopardy, which forces Brainy and Dreamer to go back in time once more to create a new course for the fateful encounter with the poachers.
After getting a sample of Kara's DNA, the Super Friends set out for the Phantom Zone; however, a Phantom causes them to see Fear Visions, in which everyone experiences their worst fear.
Flashbacks of past traumatic events cast a shadow over Kara's life upon her return to Earth, while Zor-El accompanies her and Nia to CatCo, pretending to be Kara's uncle.
As Kelly gets tasked with helping an alien boy with superpowers, she and Kara discover that his work release plan has been tampered with in order to exploit him along with other aliens.
As Supergirl tries to save the building where Joey is supposed to live with Orlando, Mitch, Naxim Tork's former partner, captures Nyxly in order to use her to catch Supergirl, whereupon Nyxly sets out to destroy the building and freezes Supergirl.
After Mxy gets summoned by Supergirl, Nyxly tries to use her to gain power in order to take revenge on her father. Elsewhere, Lena arrives at her mother's hometown, seeking to learn the truth about her.
Following the destruction of the Ormfell building, Councilwoman Rankin receives an experimental treatment that makes her gain strange powers stolen from the fifth dimension, whereupon Kelly stands up to her.
After Kara and Lena find out about the Totem of Courage, Nyxly tries to steal it, but Kara fights her, and they each end up with half of it. However, the division of the totem causes trouble, which forces Kara to release her half, but things don't go well.
As Nyxly gets her hand on the Totem of Humanity, chaos ensues. In the meantime, William helps Lena cast a magic spell for the first time.
When William is kidnapped by Nyxly, Supergirl must rescue him and stop Nyxly from getting all the totems. Due to Esme's ability to gain the superpowers of those around her, her life with Kelly and Alex starts to suffer.
Nia is forced to team up with her sister Maeve to stop Nyxly from acquiring the Dream Totem. On the other hand, Kara finds herself overwhelmed as she tries to settle matters between Kaznia and Corto Maltese.
After Lex resurfaces and teams up with Nyxly, Kara and the Super Friends find themselves forced to confront both of them together. Meanwhile, the team celebrates as Alex and Kelly get engaged.
Following their defeat at the hands of J'onn and Supergirl, Lex and Nyxly run away, and Supergirl acquires the new Hope Totem, after which Lex and Nyxly kidnap Esme and kill William.
Lex asks for the totems in order to return Esme, whom Nyxly does not want to hurt and eventually returns. Upon the formation of the Allstone, Esme causes it to shatter, leading to a fight between Nyxly, Lex, and the Superfriends over its pieces.
With Kelly and Alex's big day drawing near, Many allies join forces with the Super Friends to take down Lex and Nyxly.