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.
A thief who has psychic powers attacks National City, immobilizing victims by tapping into their worst fears; James and Lena are at an impasse; Samantha starts her new job at L-Corp.
Eliza throws Alex and Maggie a wedding shower; Maggie reaches out to her estranged father; Supergirl joins J'onn on a personal mission.
Kara investigates a new group that has a mysterious connection to Supergirl; Samantha feels like she's letting Ruby down; J'onn confesses an old secret.
Morgan Edge blames Lena's lead bomb when multiple children get sick; Kara teams up with Samantha to clear Lena's name; Alex and Maggie make a decision about their relationship.
Kara and Alex head home to Midvale for a little rest; Kara recalls a painful childhood memory that brought the Danver sisters closer together.
Kara investigates when an alien ship crash lands deep underwater beneath National City; Hank attempts to bond with his father; Samantha looks to her estranged mother for answers.
Barry and Iris' wedding brings the gang together, but things go awry when villains from Earth-X attack the ceremony.
Supergirl learns that a mysterious symbol popping up in the city is the mark of the World Killer, Reign; tension between Lena and Morgan Edge continues to build.
Struggling to heal from her injuries inflicted by Reign, Supergirl remains in a dreamlike state, unable to be reached; Mon-El recruits a Legion member to try bringing her back; the DEO teams up with the Legion of Superheroes to try to stop Reign.
Supergirl teams up with Saturn Girl, Livewire and Psi to recover a prisoner who has information on how to defeat Reign; Alex baby-sits Ruby.
Kara steps in to help Lena when she is threatened by Morgan; Alex decides to run medical tests to see if she can help Sam.
When the DEO captures a second Worldkiller, Supergirl and Alex use very different methods of interrogation in an effort to learn how to defeat Reign; J'onn, Winn and Mon-El band together to fix the Legion ship.
When Winn's father dies, his estranged mother tries to reconnect and explain why she abandoned him; a copycat Toyman attacks and the two must work together to stop him; Mon-El tells Kara something important about the Worldkillers.
Myr'nn inadvertently causes psychic disturbances at the DEO; Supergirl must work with J'onn to contain the chaos; Mon-El begins training Kara in fighting techniques he's learned in the future.
Supergirl and Imra have different ideas on how to stop the third Worldkiller, Pestilence; Pestilence seriously injures both Alex and Winn, Supergirl and Imra team up to stop the destruction.
Still reeling after learning Lena's secret, Supergirl asks Guardian for a favor that could alter his relationship with Lena forever; 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.
When 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 threatens to expose James if he doesn't do what is asked of him.
Supergirl is stunned to learn that a part of Krypton survived; Alex is attacked while out with Ruby; Lena considers how far she will go to keep Reign contained.
Kara makes a major life decision; J'onn discovers that special DEO-caliber guns have hit the streets of National City.
After learning the true depth of Serena's nefarious plans for Earth, Supergirl, Mon-El and Alura must come up with a plan to stop her; J'onn prepares to say goodbye to his father.