As National City prepares to unveil a statue in Supergirl's honor, Kara's attempts to cope with the loss of Mon-El isolates her from her friends and family -- and a new enemy prepares for a deadly strike on the city.
Kara faces her deepest fears when she takes on a psychically powered thief wreaking havoc on National City. Elsewhere Samantha Arias's daughter Ruby tries to put her mother's powers to the test, and Lena Luther clashes with the Catco staff when she takes control.
When J'onn receives a telepathic summons from M'gann he and Supergirl travel to Mars, where the White Martian resistance movement needs his help getting through to a Green survivor -- J'onn's own father. Maggie reaches out to her estranged father on the eve of her wedding shower.
Kara discovers a new religious cult where the followers all have a connection to Supergirl. Meanwhile Samantha juggles her new job and being there for her daughter.
After several children fall ill from lead poisoning Morgan Edge publicly blames Lena and the weapon that forced the Daxamites to leave. As Kara and Samantha team up to clear their friend's name, Alex and Maggie's relationship reaches a crossroads.
Kara and Alex return home to Midvale, where they remember a painful memory of a childhood friend's death and the events that solidified their bond as sisters.
The discovery of an alien ship crashed deep beneath National City leads to more shocking revelations when Mon-El is found on board. As Kara tries to reconnect with him, J'onn helps his father take his first steps outside of the confines D.E.O. Elsewhere, Samantha sets out on a personal quest to discover the source of her powers.
Kara and Alex travel to Earth-1 to attend the much-anticipated wedding of Barry Allen and Iris West, where they cannot get too far from their own relationship issues. But when an unknown group of criminals attack the festivities, they must join forces with Earth's mightiest heroes.
While tensions continue to mount between Lena and Morgan Edge, the appearance of a mysterious symbol all over National City points to the arrival of another Kryptonian. And Kara is unsettled when she learns of an ancient prophecy about the Worldkiller, Reign.
Reign's reign of destruction continues as she targets National City's criminals with a brutal sense of justice. But with Supergirl gravely wounded and trapped inside her own mind, Mon-El and his comrades resist intervening.
Supergirl and Imra recruit a pair of super-powered criminals for a mission to Fort Rozz, now in orbit of a blue star, where they hope to find information about Reign's plans. Alex volunteers to watch Ruby, and must deal with personal issues for both of them.
Morgan Edge survives an attempt on his life and blames Lena Luthor -- making him the prime suspect when Lena herself is attacked. Alex tries to help Sam find answers after she realizes that she is losing time.
The D.E.O. captures Julia Freeman, who Kara suspects is the second Worldkiller -- but Kara and Alex clash over whether or not to treat her as an enemy hostile. Winn and J'onn try to help Mon-El repair the Legion ship's power source, but find that his problems run deeper.
After the death of his criminal father Winn's estranged mother returns after twenty years -- but it soon becomes clear that the Toyman's vengeance may be reaching out from beyond the grave. Alex visits J'onn and and his father at home, but grows concerned about Myr'nn's recent behavior.
Myr'nn's struggle to maintain his mental discipline causes psychic disturbances throughout the DEO. Lena confronts Sam about her transformation, and Mon-El trains Kara to fight using her cape.
An outbreak connected to the third Worldkiller, Pestilence, pits Supergirl and Imra against one another when they believe different strategies are necessary. Lena tries to help Sam learn more about Reign.
The D.E.O. team struggles with trust issues after discovering Lena's secret, and Supergirl leads a team into a realm where they hope to find Sam's suppressed consciousness -- setting up an epic battle against Reign and the Worldkillers. James considers whether or not he can break Lena's trust when Supergirl asks Guardian for a favor.
When Reign goes on the hunt for Ruby Alex searches out the hiding place where Lena has sent the young girl, while Supergirl and J'onn pay a visit to Sam's mother to try and protect her. The Legion prepares to depart Earth.
A former disciple of Coville delivers a dire warning to Supergirl: the cult is searching for a way to create another Worldkiller. When the other cultists come looking for the girl Guardian's identity is exposed while protecting her, while Alex meets resistance in her attempts to help Ruby.
When Supergirl and Mon-El investigate a nearby meteor they discover a Kryptonian city on the surface -- her own home of Argo, where Kara's mother is alive and well. Back on Earth Alex is targeted by an assassin.
With Reign's threat to Earth apparently contained Kara decides to move home to Argo City -- unaware that the Dark Priestess cult is not yet finished with their endgame. J'onn learns that a version of the D.E.O.'s powerful weapons have hit the streets of National City.
Serena leads the Dark Priestesses in attacking the D.E.O., hoping to find what they need to resurrect Reign -- while Kara and Mon-El are trapped on Argo. J'onn and his father begin the Martian ritual that will preserve all of M'yrnn's memories and life experience.
As the D.E.O. and its allies take on Serena's forces, M'yrnn attempts to trap Reign -- and Sam fights to survive in the underworld. Guardian considers revealing his secret identity, and Brainiac approaches Winn with a stunning proposal.
