When a new threat emerges in National City, Kara/Supergirl teams up with her cousin, Clark Kent/Superman, to stop it. Kara is thrilled to have family in town but it leaves Alex feeling a bit left out. Meanwhile, Hank and Supergirl are stunned by the pod that came crashing to Earth.

CADMUS attacks National City with a Kryptonite-powered villain who ends up seriously hurting Supergirl. Superman blames Hank because the Kryptonite was stolen from the DEO. Meanwhile, Kara’s first day at her new job doesn’t go as planned after she meets her new boss, Snapper Carr.

Supergirl must beat a ruthless new gang who has been armed with dangerous new alien technology. When Cadmus sends a video to the DEO, the team realizes Cadmus is the one staffing the criminals for a secret mission. Meanwhile, Kara gets Mon-El a job as an intern at CatCo, James makes an important decision and Lena invites Kara to attend one of her fundraisers.

The Guardian debuts to lend a hand after a parasite alien drains Supergirl of her power. Mon-El considers a less than desirable new career which then leads him to contemplate his motives. Alex struggles with a new reality.

While Guardian tries to clear his name after being accused of a murder committed by another vigilante, Supergirl heads out on a solo mission to rescue Mon-El who has been captured by Cadmus. While fighting to free Mon-El, Supergirl comes face to face with Cyborg Superman.

Eliza comes to town to celebrate Thanksgiving with her daughters. Alex decides it’s time to come out to her mother; Kara is shocked when Eliza suggests Mon-El has feelings for her, and Winn and James consider telling Kara the truth about the Guardian. Meanwhile, Cadmus unleashes a virus that instantly kills any alien in the vicinity so Kara enlists an unexpected ally – Lena Luthor. The epic superhero crossover kicks off tonight when Barry Allen and Cisco Ramon seek Kara's help with an alien invasion on their Earth.

The crossover continues on The Flash S03E08 Invasion! (II), Arrow S05E08 Invasion! (III) and DC's Legends of Tomorrow S02E07 Invasion! (IV).

Efter Metallo bryder ud og befrier Lillian Luthor, anholder politiet Lena Luthor, men Kara nægter at tro, at hendes ven er skyldig, og hun kæmper for at rense hendes navn.

When Jeremiah Danvers is rescued from Cadmus, Alex and Kara are thrilled to have their father back. The Danvers arrange a family dinner to celebrate but things go awry when a suspicious Mon-El starts to question Jeremiah about his sudden return.

As Alex searches for Jeremiah and Kara investigates a series of alien kidnappings, the sisters realize they must break the rules to foil a new Cadmus plot. In an effort to get Snapper Carr to run a story that would help her stop Cadmus, Kara agrees to set up an interview between Snapper and Supergirl.

Supergirl grapples with whether or not to obey the President's orders regarding Rhea's latest actions. Meanwhile, Cat Grant returns to National City.

Supergirl challenges Rhea to battle to save National City. Meanwhile, Superman returns and Cat Grant offers Supergirl some sage advice.

Someone tries to kill Morgan Edge and he barely survives. He accuses Lena of being behind the attempt and vows to destroy her. When Lena fears her hatred for Morgan will take her to the Luthor dark side, Kara steps in to help her friend. Meanwhile, after Sam realizes she’s losing time, she confides in Alex who decides to run some medical tests to see if she can find out what’s going on with her new friend.

Diving back into reporting, Kara welcomes a new cub reporter to CatCo. Meanwhile, James and Lena argue about James’ impending indictment for acting as the vigilante Guardian, while Alex and Brainy struggle to get in sync at the DEO. Supergirl is called into action when remnants of the anti-alien terrorist organization Cadmus try to assassinate pro-alien leaders, but their endgame turns out to be much more sinister than she expected. J’onn relishes his peaceful new life, but an outing with an old friend causes him concern.

Supergirl must deal with the destructive aftermath of Lex's nefarious plans. Shocked at what Lex has created, Supergirl faces her biggest challenge yet.

Kara comes face to face with Red Daughter and the two engage in an epic battle. Determined to find a way to extract the Harun-El, Lena turns to an unlikely source for help - Lillian Luthor. Meanwhile, Alex realizes she's missing parts of her memory, and Brainy, Nia and J'onn set out to track down aliens who have been abducted by Lex.

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.

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

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.

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 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 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.