Kelly is horrified when the Ormfell building implodes, injuring many in the community, including Joey. However, her horror quickly turns to frustration when she realizes that the hospital is overwhelmed, people are getting sicker, and no one is coming to help - including Supergirl who is busy fighting Nyxly. Knowing that she can make a difference, Kelly embraces her power and fully steps into her role as Guardian. Joined by Supergirl, Alex, Diggle and team, Guardian leads the way to restoring justice to the fallen community.

Lex tasks Supergirl with protecting Andrea from an anti-tech extremist, but his nefarious purpose goes beyond merely keeping Andrea alive. Meanwhile, Lena moves forward with Non Nocere, with Lex’s help.

Nia’s roommate, Yvette, is attacked by a man targeting Dreamer because he doesn’t like that Dreamer is transgender and wants her to quit being a superhero. Determined to protect her community from additional harm, Dreamer refuses to give into his threats and puts herself in the line of fire to stop him. Supergirl stands by Dreamer and enlists additional help from Brainy. Meanwhile, Alex, J’onn and Kelly attempt to rescue a man stuck inside a virtual reality escape room.

Supergirl intervenes when a building in the Heights that was set aside for low income housing is suddenly at risk to be sold to a major corporation. Supergirl recruits Orlando to help her win over the city, but things go awry when Nyxly shows up. Meanwhile, Nia trains with her mother.

Kara lands her dream story for Catco but when the city is suddenly attacked by a nightmare monster at the same time as her interview, she is forced to take a serious look at her life and decide if she can continue to live as both Kara and Supergirl. As Dreamer takes the lead on the search for the Dream Totem, which can vanquish they nightmare monster in National City, she realizes she needs to ask her sister Maeve for help.

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

Supergirl is determined to keep everyone safe from Lex and Nyxly so she doubles down on patrol, especially as Alex and Kelly's bachelorette party is coming up. Alex is torn between duty and finally allowing herself the time to enjoy her new family. Brainy receives heartbreaking news, and William clashes with Andrea over her recent coverage of Lex.

Supergirl and the super friends take drastic action after a loved one is kidnapped by Nyxly and Lex. An unlikely ally steps in to help the team.

Supergirl is joined by familiar faces from the past to help her stop Lex and Nyxly for good. Meanwhile, Alex and Kelly prepare to walk down the aisle.

Supergirl helps Winn face his greatest fear. After Alex sets out to find evidence against Lex, Brainy must decide between helping his friend or continuing to secretly work for Lex.

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.

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.

Supergirl, Alex, and Brainiac thwart an alien attack while William investigates Kara. J'onn J'onzz and Kelly use Obsidian tech to solve a problem.

As Supergirl tries to thwart a Toyman copycat, Winn Schott returns from the future.

As the Super Friends brave the Phantom Zone to bring Supergirl home, each member of the team is confronted by visions of their worst fear.

Kelly meets Joey, a young orphaned alien boy, who is acting out in foster care because he fears there is something wrong with his brother Orlando, who is incarcerated. Kelly asks Kara to help her investigate and they stumble upon abuse at the prison. Meanwhile, Nyxly crashes one of Nia's dreams and asks her for help.

Kara's investigation into William Dey's "criminal" activities results in the shocking revelation he is not who she thinks. Meanwhile, the conflict between Malefic and J'onn J'onzz reaches a boiling point.

Supergirl continues to fight Nyxly for the remaining totems but after Nyxly kidnaps William, Supergirl realizes she needs to take a more proactive stance to keep National City safe. Meanwhile, Alex faces the biggest challenge of her life.

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.

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.

On the eve of the worldwide launch of Andrea Rojas's VR contact lenses, Kara and William team up on an investigation that exposes a terrorist plot. Kelly and Alex celebrate an anniversary, but Alex's safety is in jeopardy.

As Supergirl and Zor-El make their return to National City, they are determined to keep the Phantom Zone behind them and enjoy being superheroes together. Unfortunately, their overzealous efforts backfire, creating a whole new threat to National City.

Supergirl and team must stop Nyxly from vanquishing a familiar face from Supergirl's past - Mr. Mxyzptlk. Mxy returns and explains Nyxly's dark history to the super team in the best way he knows how - in song form. Meanwhile, Lena visits her mother's birthplace in Newfoundland, eager to dig into her past but is shocked by the small town's icy reception towards her.

When Lex Luthor appears by Nyxly's side, Supergirl and team must deal with the emotional fallout of facing their two biggest foes at the same time. Alex makes plans for the perfect proposal to Kelly, but work keeps getting in the way.

When Winn’s father dies, his estranged mother, Mary, reappears trying to reconnect and to explain why she abandoned him all those years ago. Winn is too embittered from his rough childhood to forgive her but when a copycat Toyman attacks, the two must work together to stop him. Mon-El tells Kara something important about the Worldkillers, and Alex becomes suspicious of Myr'nn’s recent behavior.