After 12 years of keeping her powers a secret on Earth, Kara Zor-El, Superman's cousin, decides to finally embrace her superhuman abilities and be the hero she was always meant to be.

Kara's Thanksgiving may be ruined when she suspects her foster mother, Dr. Danvers, who is coming to town, disapproves of her new role as a superhero. Also, when an accident transforms a volatile CatCo employee into the villainous Livewire, she targets Cat and Supergirl.

Kara must find a way to free her friends when Non and Indigo use mind control to turn National City’s citizens into their own army.

Supergirl is forced to do battle with an unexpected foe and must risk everything – including her life – to prevent Non and Indigo from destroying every person on the planet.

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).

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.

Eliza throws Alex and Maggie a wedding shower, which causes Maggie to reach out to her estranged father. Supergirl joins J’onn on a personal mission.

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 Danver sisters closer together.

Everyone gathers for Thanksgiving but Kara is feeling down after her televised debate with Ben Lockwood about the anti-alien sentiment coursing through National City. Meanwhile, James and Lena argue about the best way to handle the Children of Liberty.

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.

Alex uses a pair of Obsidian contact lenses to visit a virtual National City where she takes on a whole new persona. Meanwhile, Kelly helps William investigate Lex. Kara deals with difficult news.

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.