Kara deals with the loss of Mon-El by focusing her energy on being Supergirl and concentrating on a mysterious new threat. Alex confesses a secret to Maggie. A citizen of National City has a mysterious connection to Kara. Lena makes a bold move.
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.
Kara and Alex head home to Midvale for a little R&R. While there, Kara recalls a painful memory of a childhood friend's death and how that traumatic experience brought the Danvers sisters closer together.
Kara investigates when an alien ship lands deep underwater beneath National City; Hank attempts to bond with his father; Samantha looks to her estranged mother for answers.
Supergirl remains in a dreamlike state after sustaining injuries from Reign, so Mon-El recruits Brainiac-5, a member of the Legion of Superheroes, to bring her back.
Supergirl must work with J'onn to contain the chaos resulting from Myr'nn's psychic disturbances at the DEO; Mon-El teaches Kara fighting techniques he learned in the future for battling Worldkillers.
Supergirl and Imra have different ideas on how to stop the third Worldkiller, Pestilence. However, when both Alex and Winn are seriously injured by Pestilence, Supergirl and Imra team up to stop the destruction.
Still reeling after learning about Lena's secret, Supergirl asks Guardian for a favor that could alter his relationship with Lena forever. Meanwhile, with all three Worldkillers united, Supergirl and the team brace for an epic battle.
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 shocking news.
Supergirl is stunned to discover that a part of Krypton survived. Meanwhile, Alex is attacked while out with Ruby, and Lena considers how far will she go to keep Reign contained.
Supergirl learns the true depth of Selena's nefarious plans for Earth. Supergirl, Mon-El and Alura must devise a plan to stop her before Selena gets to Earth. J'onn prepares to say goodbye to his father.