Kara investigates a secretive new group whose leader, Thomas Coville, has a mysterious connection to Supergirl. Meanwhile, Samantha feels like she's letting Ruby down, and J'onn confesses an old secret.

Supergirl investigates a mysterious symbol popping up all over National City, tracing its origins back to an ancient prophecy and the mark of the World Killer, Reign. Meanwhile, the tension between Lena and Morgan Edge continues to build, causing James to step in and offer up some protection, and possibly igniting a spark in the process.

Struggling to heal from her injuries inflicted by Reign, Supergirl remains in a dreamlike state, unable to be reached. Mon-El recruits one of the Legion members, Brainiac-5, to try to bring her back. Meanwhile, Reign continues her rampage on the city so the DEO teams up with the Legion of Superheroes to try to stop her.

When Tanya, a disciple of Coville's, escapes from what's left of his cult, she gives Kara and James a journal that could hold the key to saving Sam. Someone learns Guardian's identity and threatens to expose James if he doesn't do what they ask. James contemplates what it means to be a black vigilante without a mask in America.

Kara makes a major life decision. Meanwhile, J'onn finds out that special DEO-caliber guns have hit the streets of National City.

Supergirl learns the true depth of Serena's nefarious plans for Earth. Supergirl, Mon-El and Alura must devise a plan to stop her before Serena gets to Earth. J'onn prepares to say goodbye to his father.

Supergirl and team take on Selena in an epic battle for Earth.

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.