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 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.
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. Meanwhile, Alex and Maggie celebrate their first Valentine’s Day together.
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.