Supergirl is an action-adventure drama based on the DC Comics character Kara Zor-El, Superman's (Kal-El) cousin who, after 12 years of keeping her powers a secret on Earth, decides to finally embrace her superhuman abilities and be the hero she was always meant to be.
After losing Mon-El, Kara decides to give up her human life and dedicate herself full-time to being Supergirl. Meanwhile, a new menace threatens National City, and real estate mogul Morgan Edge makes a bid to buy up CatCo. Also, Alex confesses a secret to Maggie, a citizen of National City has a mysterious connection to Kara, and Lena makes a bold move.
Kara takes Alex home to Midvale after Alex and Maggie break up. While Alex deals with the end of her relationship, she and Kara remember the first time that they bonded as sisters while solving the murder of a fellow high school student.
When Winn and the team discover an alien ship has crash landed deep underwater beneath National City, Kara/Supergirl is called in to investigate. Meanwhile, Hank attempts to bond with his father, Myr'nn. Samantha, eager for some understanding of the changes she has been experiencing, looks to her estranged mother, Patricia Arias, for answers.
Barry and Iris's wedding brings the gang together, but things go awry when villains from Earth-X attack the ceremony. All of the superheroes band together with help from their super friends like Citizen Cold, The Ray, Felicity Smoak, Iris West and Alex Danvers to take on their most formidable villains yet. Earth's mightiest heroes – Green Arrow, Supergirl, The Flash and White Canary – lead their teams into battle to save the world.
Supergirl investigates a mysterious symbol popping up all over National City, tracing its origins back to an ancient prophecy and the mark of the World Killer, Reign. Meanwhile, the tension between Lena and Morgan Edge continues to build, causing James to step in and offer up some protection, and possibly igniting a spark in the process.