Twenty-four-year-old Kara Zor-El, cousin of Superman, who was taken in by the Danvers family when she was 12 after being sent away from Krypton, must learn to embrace her powers after previously hiding them.
A new Fort Rozz prisoner, Hellgrammite, commits a series of robberies of chemical manufacturing plants. While the DEO goes after him, Supergirl discovers that fame is fickle when the public turns against her after a series of mishaps.
Supergirl faces her first non-alien nemesis when one of her cousin's enemies--the nuclear-powered Reactron--comes looking to kill her. Meanwhile, Cat runs a derogatory exposé on Supergirl after interviewing the superhero.
Kara has her hands full dealing with her foster mother Eliza's visit as well as a new super-villain, Livewire, who is out for revenge against Cat.
Kara finds herself juggling her personal and public lives when she offers to take care of Cat's son Carter, deal with James' relationship with Lucy, and try to stop a bomber who is targeting Maxtech properties.
While Kara deals with personal pressures as both office assistant and superhero, General Sam Lane arrives in National City to field-test his new anti-insurgent android, Red Tornado... and to tell James that he's not good enough for his daughter Lucy. Meanwhile, Alex and Kara ask Winn to hack the DEO mainframe to find out how Jeremiah died, and Cat deals with her domineering mother.
Kara is still without her powers when an earthquake rocks National City. Now she and her friends must rise to the occasion. Meanwhile, the DEO's attempts to restrain an escaped prisoner are threatened by Alex's mistrust of Hank after she learns of his role in Jeremiah's death.
Astra calls Supergirl out to fight, but soon loses. However, Hank and Alex suspect that the Kryptonian general lost too easily. Meanwhile, an email hack threatens Cat's position as CEO of CatCo, and Kara learns that someone is trying to force her boss out of the company.
Supergirl tries to convince her aunt to help them recover Hank from the Kryptonians and is forced to rely on blind faith. Meanwhile, Max continues his campaign to bring down Supergirl, and Kara tries to convince Cat that she and Supergirl are not one and the same.
The Toyman--Winn's father--breaks out of prison and begins a new criminal rampage on a quest to be reunited with his son. Meanwhile, Lucy accepts a job at CatCo, much to Jimmy's discomfort.
Kara must help Hank face his painful past when a White Martian, a member of the alien race that wiped out his people, kidnaps Senator Miranda Crane, an anti-alien politician. Also, Cat's estranged son, Adam, arrives in National City.
Max creates a reverse image of Supergirl using her DNA, and sets it to fight the Woman of Steel. Meanwhile, James and Winn share a drink, and Max reveals to Alex how much he knows about her connection to Supergirl.
Supergirl is ensnared by an alien plant that forces her into her deepest desire, and her friends and sister must free her before it's too late. Meanwhile, the Kryptonians launch their plan to bring humanity to its knees and save Earth.
An armored alien with advanced tech is hunting down the Fort Rozz prisoners... and executing them. While Supergirl tries to find him, James questions whether the DEO has the right to lock up Max without charges or a trial. Meanwhile, Kara tries to deal with Cat's new assistant at work, who is intent on upstaging Kara.
A new enemy emerges to threaten Supergirl and National City... and has a connection to Krypton. Meanwhile, Lucy demands the truth from James, and Kara continues refusing to work with Hank, unaware that Alex is the one who killed Astra.
After defending Supergirl to the public, Cat is forced to issue a public warning after exposure to Red Kryptonite turns Supergirl into a power-mad villain.
A captive Hank tells the U.S government how he came to lead the DEO, but receives a less than sympathetic ear. Meanwhile, Kara reveals her identity to someone close to the investigation, and Siobhan plans revenge Kara for getting her fired from CatCo.
Supergirl finds herself in a super team-up when a new superhero, The Flash, accidentally crosses dimensions and finds himself in Kara's universe. Together they have to battle Livewire and a new villainess, Silver Banshee.
Kara must find a way to free her friends when Non and Indigo use mind control to turn National City's citizens into their own army.
To stop Non from wiping out Earth's population, Supergirl has no choice but to sacrifice her life. Before she does so, Kara says goodbye as best she can to her friends without telling them the truth and inciting a panic.