Barry and Iris’s wedding brings the gang together, but things go awry when villains from Earth-X attack the ceremony. All of the superheroes band together with help from their super friends like Citizen Cold, The Ray, Felicity Smoak, Iris West and Alex Danvers to take on their most formidable villains yet. Earth’s mightiest heroes – Green Arrow, Supergirl, The Flash and White Canary – lead their teams into battle to save the world. The crossover continues on Arrow S06E08 Crisis on Earth-X (II), The Flash S04E08 Crisis on Earth-X (III) and DC's Legends of Tomorrow S03E08 Crisis on Earth-X (IV).

Kara turns on her friends and the citizens of National City after being exposed to Red Kryptonite makes her malicious and dangerous. Also, Cat appears on THE TALK to discuss Supergirl.

Kara gains a new ally when the lightning-fast superhero The Flash suddenly appears from an alternate universe and helps Kara battle Siobhan, aka Silver Banshee, and Livewire in exchange for her help in finding a way to return him home.

Supergirl investigates a mysterious symbol popping up all over National City, tracing its origins back to an ancient prophecy and the mark of the World Killer, Reign. Meanwhile, the tension between Lena and Morgan Edge continues to build, causing James to step in and offer up some protection, and possibly igniting a spark in the process.

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.

Supergirl, The Flash, Green Arrow and Superman engage in the battle of their lives. The crossover starts on The Flash S05E09 Elseworlds (I) and Arrow S07E09 Elseworlds (II).

The Monitor sends Harbinger to gather the worlds’ greatest heroes - Supergirl, The Flash, Green Arrow, Batwoman, White Canary, The Atom and Superman - in preparation for the impending Crisis. With their worlds in imminent danger, the superheroes suit up for battle while J’onn and Alex recruit Lena to help them find a way to save the people of Earth-38. This crossover continues on Batwoman S1E09, The Flash S6E09, Arrow S8E08, and Legends of Tomorrow S05E01.

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.

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.

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.

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.

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.

J'onn J'onzz reveals the details of meeting Kara and Alex's father, Dr. Jeremiah Danvers, and assuming Hank Henshaw's identity. Also, Kara debates trusting someone new with her secret identity and Siobhan plots against Kara.

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.

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.

Kara and her friends must rely on their inner strength and courage when an earthquake strikes National City. Also, Alex’s mistrust of Hank reaches a breaking point when the earthquake traps them in the DEO with Jemm, a powerful alien escapee.

Kara goes toe-to-toe with Astra when her aunt challenges Kara’s beliefs about her mother. Also, Cat is threatened with being removed as the CEO of CatCo after a hacker exposes her private and damaging emails.

Kara must help Hank face his painful past when a White Martian, a member of the alien race that wiped out his people, kidnaps Senator Miranda Crane, an anti-alien politician. Also, Cat's estranged son, Adam, arrives in National City.

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).

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

Kara’s friends must find a way to save her life when a parasitic alien attaches itself to her and traps her in a dream world where her family is alive and her home planet was never destroyed. Also, Alex, Hank and the DEO must fend off a Kryptonian attack while Kara is out of commission.

After Metallo breaks out of prison and frees Lillian Luthor, the police blame Lena for his escape and arrest her. Despite overwhelming evidence, Kara refuses to believe her friend is guilty and fights to clear Lena’s name. Flashbacks reveal how Lena came to be a Luthor.

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.

An attack is made on the President as hot-button, alien vs. human rights issues heat up in National City. Supergirl and the DEO are assigned to protect the President and bring in the responsible party. Alex teams up with Detective Maggie Sawyer to investigate the case while Kara searches for a recently escaped Mon-El, who she fears may be the alien behind the assault.