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.

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.

When Kara and Alex investigate the murder of an unregistered alien, the trail leads to an alien fight club run by Roulette, the ringmaster who commands aliens to fight in mortal combat for the entertainment of rich humans. While trying to stop the fighting, Supergirl and Martian Manhunter find themselves up against a surprising opponent. Meanwhile, Hank is thrilled to have found another Martian and tries to get to know M'Gann better. Supergirl takes Mon-El under her wing and begins to train him.

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).

Kara is moved by the story of a missing woman named Izzy and decides to investigate despite Snapper Carr's order to leave it alone. Kara takes Mon-El with her to the last place Izzy was seen and the duo find themselves thrust through a portal to another planet, Slaver's Moon, where the downtrodden are sold as slaves. The leader of the trafficking ring is none other than Roulette. To make matters worse, Slaver's Moon has a red sun, which means Kara and Mon-El are stripped of their powers and stuck on the planet with no way home. Meanwhile, back on Earth, Alex blames herself for Kara's disappearance, fearing she's become too focused on her new relationship with Maggie and too complacent in watching out for her sister.

After Livewire seemingly breaks out of prison, Supergirl is intent on recapturing her. After training Mon-El, Supergirl takes him with her when she sees Livewire attack the NCPD but things go awry when Mon-El puts Supergirl before the citizens of National City. Meanwhile, James decides to come clean with Kara and M’Gann, has a psychic attack and collapses into a coma.

Armek, a White Martian, descends on National City intent on taking M’gann back to Mars to face her punishment as a traitor. Hank and Supergirl determine the best way to keep M’gann safe is to bring her to the DEO. However, when it is revealed that Armek shape-shifted into M’gann and is now loose in the building, the team realize he could be disguised as any one of them.

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.

When Mr. Mxyzptlk, a magical imp, shows up on Earth and declares his love for Kara, she tries to let him down easy, thinking him harmless. However, he decides it’s a challenge and starts to wreak havoc on National City. Mon-El has seen beings like Mr. Mxyzptlk on Daxam and knows how dangerous they can be. He and Kara argue over how to get rid of Mr. Mxyzptlk, further straining their relationship. Meanwhile, Alex and Maggie celebrate their first Valentine’s Day together.

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.

A new villain comes to National City, putting Supergirl on high alert. Meanwhile, Winn’s girlfriend, Lyra, gets Winn in trouble with the law. Maggie attempts to help Winn but old loyalties get in the way. The Music Meister attacks Supergirl.

The crossover continues on The Flash S03E17 Duet (II).

A large bounty is put out on Supergirl and aliens from far and near attack National City intent on taking out the woman of steel. Alex and Maggie run into Maggie’s ex-girlfriend, Emily, who is in town for a week. Hank gets an interesting order from President Marsdin.

Lena’s ex-boyfriend, Jack Spheer, comes to National City to unveil his big breakthrough in nano-technology, which has the potential to eradicate all diseases. Lena asks Kara to attend Jack’s conference with her for support. When Kara sees Snapper in attendance she’s inspired to tap back into her reporter skills and questions Jack on his discovery, which ultimately leads to a bigger investigation that puts everyone in danger.

Alex is kidnapped and the kidnapper threatens to kill her unless Supergirl releases a notorious criminal from prison. Supergirl and Maggie have always had different approaches to apprehending criminals but this time they must work together to save Alex. Meanwhile, Rhea has an interesting proposal for Lena.

When an alien attacks National City, Supergirl and the DEO learn the alien is a Phorian, an otherwise peaceful race with telekinetic powers. Guardian gets a lead on the Phorian's address but instead of finding the culprit, he finds a very scared boy named Marcus. Marcus will only trust James so it is up to Guardian to stop the attacks on the city. Rhea's plan escalates.

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.

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.

A shocking revelation causes chaos in National City. Supergirl sets out to capture Mercy Graves, while Alex takes control at the DEO. Back at CatCo, Kara decides to write an investigative story on Mercy and asks Lena if she can interview her as Mercy has ties to the Luthors. Meanwhile, Brainy meets Nia and the two end up in a precarious situation.

Ben Lockwood didn't always hate aliens. Through a series of incidents, and input from his anti-alien father, Ben slowly transforms from a mild-mannered professor into the villainous Agent Liberty of today.

When Supergirl needs help, Alex asks Lena and Brainiac to team up. Meanwhile, J’onn questions his decision to quit the DEO. However, after running into Manchester Black, he realizes there are a lot of ways to help his fellow aliens during this tumultuous time.

Colonel Haley makes a surprising decision regarding Supergirl. Kara writes a series of articles highlighting aliens in National City in the hopes that humans will stop being so fearful of them. Unfortunately, the article puts some of the aliens in harm’s way.

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.

James falls in deeper with the Children of Liberty in his efforts to meet Agent Liberty. Meanwhile, Supergirl and Manchester Black follow a lead on Agent Liberty’s location, but things take a dark turn. Lena kicks off her first set of trials.

Nia has a powerful dream about Agent Liberty but refuses to look at it as a prophetic dream and pushes it aside. After noticing something is bothering Nia, Kara enlists Brainy's help, and the two try to persuade Nia to embrace her destiny. Meanwhile, Manchester Black pays Ben Lockwood a menacing visit.

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).

Colonel Haley is upset after Supergirl responds to a distress call from a Navy ship that turned out to be a deadly alien attack. Colonel Haley reclaims the site as DEO territory and demands that Supergirl step aside. After Supergirl refuses to be told what to do, Haley refocuses her energy on finding out Supergirl's true identity and begins to interrogate all DEO agents, including Alex. Meanwhile, Brainiac-5 tries to persuade Nia to embrace her superpowers but she misinterprets his motives.

Kara joins Nia on a trip to Nia's hometown to visit her family during the town's annual Harvest Festival. While home, Nia's mother encourages her daughter to embrace her destiny. Meanwhile, Alex deals with a street drug that is turning people violent and giving them temporary superpowers.

With his P.I. shingle newly hung outside his office, J'onn welcomes new clients. Trying to take her mind off what happened at the DEO, Kara decides to team up with J'onn on his latest assignment, which unfortunately ends up tying directly into Alex's current investigation that involves the villain Menagerie. Meanwhile, Lena shares some news with James, but his reaction isn't what she expected. Nia invites Brainy to her Valentine's Day party.

Manchester Black breaks out of prison with the help of his new team, The Elite, who are set on punishing the anti-alien forces. Supergirl pulls double duty as she tries to apprehend Manchester Black and his team as well as deal with a shocking new development with Ben Lockwood.

Between Ben Lockwood’s new push to stir up the anti-alien movement and the Elite’s desire to target Lockwood and his minions, Supergirl is concerned about the safety of the American people – both human and alien. When Lockwood organizes a rally, the aliens decide to peacefully protest. Brainiac and J’onn join the alien march while Supergirl and Dreamer patrol to keep everyone safe. Meanwhile, James picks up his camera again to cover the march for CatCo, and Hayley assigns Alex a job that clashes with her beliefs. When The Elite and Ben Lockwood stir up trouble at the rally, Supergirl is forced to take a stand.

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.

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 and Lena head to Stryker's Island to search for clues on how to defeat Lex. At the prison, Kara tries to befriend a nosy prisoner, Steve, who may have insight into what Lex was doing, while Lena studies an array of puzzles Lex left behind in the hopes of discovering his whereabouts. While there, a prison riot breaks out and Kara must find a way to stop the prisoners without revealing her secret identity as Supergirl. Meanwhile, Kelly encourages James to talk to someone for his PTSD, and Alex faces off against Ben Lockwood after he storms the DEO and acquires some powerful weapons to hunt Supergirl.

As Kara doggedly works as a reporter to clear Supergirl's name, Dreamer picks up the slack as National City's protector, which leads to a showdown with Ben Lockwood. James takes drastic measures to relieve his PTSD.

Kara and Lena head to Kaznia to hunt down Lex. However, Eve Tessmacher sets a trap for the duo that could ultimately reveal that Kara is Supergirl. Meanwhile, Alex gets a long-awaited phone call, James practices using his powers, and Ben Lockwood takes a dangerous stand inside the DEO.

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.