Secretly furloughed from prison due to failing health, Lex Luthor visits his sister, Lena, to seek her help finding a cure. Savvy as ever, Lena is suspicious of Lex's motives but when she's faced with a life and death situation, she must decide how she truly feels about her brother. Meanwhile, Supergirl and J'onn face off against Manchester Black. James' sister Kelly comes to town.

In the wake of Lex Luthor's return, the show flashes back to what he's been doing for the last two years and how his secret machinations and plans have affected Supergirl and Lena.

Lex Luthor descends upon Washington, DC and summons Lena and Lillian Luthor to the White House. Supergirl realizes she has one last chance to stop Lex and turns to the power of the press to help her.

While a new villain is under arrest at the DEO, Supergirl uses him to try and understand who is responsible for the recent attacks. Meanwhile, Andrea and Lena think back on their tumultuous past.

Supergirl's struggle against Leviathan reaches a boiling point as she faces off against Rama Khan. Meanwhile, as Lena and Hope work to launch Project Non Nocere, Hope proves to be an invaluable asset to Lena.

The subsequent complications from the Crisis leave Supergirl to face a chaotic threat.

As Supergirl tries to thwart a Toyman copycat, Winn Schott returns from the future.

Supergirl helps Winn face his greatest fear. After Alex sets out to find evidence against Lex, Brainy must decide between helping his friend or continuing to secretly work for Lex.

Lex tasks Supergirl with protecting Andrea from an anti-tech extremist, but his nefarious purpose goes beyond merely keeping Andrea alive. Meanwhile, Lena moves forward with Non Nocere, with Lex’s help.

Lex proceeds to lay an intricate plan to bring Lena closer to him, defeat Leviathan’s latest attack, and pit Supergirl and team against Leviathan. It is also revealed how Lex came into power after Crisis.

Supergirl and the team go head to head against Rama Khan and Leviathan. Meanwhile, Lena and Lex must join forces when Project Non Nocere fails, leaving the two siblings in serious danger.

Supergirl realizes that in order to stop Lex and Leviathan she must work with the one person she never thought she’d trust again – Lena. Nia keeps dreaming about Brainy but struggles with what the dreams are trying to tell her. Meanwhile, Brainy realizes there is only one way to stop Lex.

As Brainiac lays close to death after trying to stop Lex, Supergirl and team soar in to save him, engaging in an epic battle with Gamemnae. After beating Leviathan, Supergirl turns her attention to Lex who has used the Obsidian platform to brainwash half the world to love him and follow him at all costs, no matter what horrible things he does. Knowing how dangerous this makes her brother, Lena enlists the entire team – Alex, J’onn , Dreamer, Kelly and Brainiac – to help, but Supergirl realizes that the only way to truly stop Lex is to sacrifice herself.

As the stakes with Lex are raised higher than ever before, Lena must decide how far she is willing to go to stop her brother. Meanwhile, Supergirl and the team are faced with a challenge unlike anything they've ever dealt with before and it brings Alex to her breaking point.

Supergirl makes a new ally. Lena and Lex battle for control of Luthor Corp.

Kara lands her dream story for Catco but when the city is suddenly attacked by a nightmare monster at the same time as her interview, she is forced to take a serious look at her life and decide if she can continue to live as both Kara and Supergirl. As Dreamer takes the lead on the search for the Dream Totem, which can vanquish they nightmare monster in National City, she realizes she needs to ask her sister Maeve for help.

When Lex Luthor appears by Nyxly's side, Supergirl and team must deal with the emotional fallout of facing their two biggest foes at the same time. Alex makes plans for the perfect proposal to Kelly, but work keeps getting in the way.

Supergirl is determined to keep everyone safe from Lex and Nyxly so she doubles down on patrol, especially as Alex and Kelly's bachelorette party is coming up. Alex is torn between duty and finally allowing herself the time to enjoy her new family. Brainy receives heartbreaking news, and William clashes with Andrea over her recent coverage of Lex.

Supergirl and the super friends take drastic action after a loved one is kidnapped by Nyxly and Lex. An unlikely ally steps in to help the team.

Supergirl is joined by familiar faces from the past to help her stop Lex and Nyxly for good. Meanwhile, Alex and Kelly prepare to walk down the aisle.