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.

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 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.

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

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.

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.

Lex proceeds to lay an intricate plan to bring Lena closer to him, defeat Leviathan’s latest attack, and pit Supergirl and team against Leviathan. It is also revealed how Lex came into power after Crisis.

Supergirl and the team go head to head against Rama Khan and Leviathan. Meanwhile, Lena and Lex must join forces when Project Non Nocere fails, leaving the two siblings in serious danger.

Supergirl realizes that in order to stop Lex and Leviathan she must work with the one person she never thought she’d trust again – Lena. Nia keeps dreaming about Brainy but struggles with what the dreams are trying to tell her. Meanwhile, Brainy realizes there is only one way to stop Lex.

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.

Supergirl makes a new ally. Lena and Lex battle for control of Luthor Corp.

Supergirl finds an opportunity to escape from the Phantom Zone but it comes with some dangerous strings attached. Meanwhile, Lena joins the Super Friends on a mission but finds she disagrees with their plan of action against the Phantoms and wonders if she is truly ready to be a part of the team.