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.

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.

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 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.

Psi, a thief with psychic powers, attacks National City. Able to immobilize people by tapping into their worst fears, Psi proves a formidable opponent for Supergirl. Meanwhile, James and Lena are at an impasse, and Samantha starts her new job at L-Corp.

When multiple children get sick from lead poisoning, Morgan Edge points the finger at Lena and blames her creation of the lead bomb she made to save National City from the Daxamites. While Lena knows she never intended any harm, she fears there may have been a flaw in her design, leaving her responsible. Kara teams up with Samantha to clear Lena’s name, but it turns out to be harder than they thought. Meanwhile, Alex and Maggie make a crucial decision about the future of their relationship.

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.

When Tanya, a disciple of Coville's, escapes from what's left of his cult, she gives Kara and James a journal that could hold the key to saving Sam. Someone learns Guardian's identity and threatens to expose James if he doesn't do what they ask. James contemplates what it means to be a black vigilante without a mask in America.

Kara makes a major life decision. Meanwhile, J'onn finds out that special DEO-caliber guns have hit the streets of National City.

Supergirl learns the true depth of Serena's nefarious plans for Earth. Supergirl, Mon-El and Alura must devise a plan to stop her before Serena gets to Earth. J'onn prepares to say goodbye to his father.

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.

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.

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.

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.

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.