Lena Luthor was named after Lex Luthor's foster sister, Lena Thorul, who was believed to be the last person to genuinely love Lex and who had been killed by their foster father, Cassy Griggs. Lex had the Contessa drugged immediately after she gave birth to Lena in order to remove her as competition for Lena's love with the intention of keeping her unconscious indefinitely at a LexCorp-owned facility. The Contessa was able to escape due to her secret immortality causing the drugs to have less of an effect on her and fakes her death, then while in hiding engages in behind-the-scenes 'custody battle' with Lex over Lena. The Contessa ultimately acquiesces and lets Lex have Lena, but she does so because she knows that Lena has inherited her immortality and she intends to simply wait until Lex has died to reenter Lena's life.
When Brainiac 13 arrives from the 64th century, the modern Brainiac possesses the infant Lena to escape it. After Brainiac 13 had been defeated and was dying, he offers Lex to leave Metropolis upgraded to his 64th century B13 technology, which would have otherwise disappeared when he died, in exchange for the body of Lena which with the modern Brainiac inside of it would allow Brainiac 13 to escape. Lex agrees to this because LexCorp had been destroyed in Brainiac 13's attack and rather than having nothing the deal would leave him more powerful than he had ever been before.
Lena returns a few years later, after having been aged to be a teenager by Brainiac 13, to visit Lex in the White House during the Our Worlds at War crossover, where she gives Lex information under the pretense of helping him and his allies beat Imperiex with the hidden intent of secretly manipulating events to benefit her master Brainiac 13. After her true intentions and allegiance to Brainiac 13 are revealed, Lex visits her and convinces her to side with him and betray her master.
At the end of the crossover, Brainiac 13 and Imperiex are both destroyed, and Lena is regressed to the infant state she had been in where she was first traded away, though now with Brainiac discs on her forehead, and returned by her father by Superman, who tells Luthor that he now has a second chance to try to be a man instead of a god. Following Our Worlds At War, Lena appears infrequently, sometimes still shown as having the Brainiac discs.
In the Superman: Metropolis miniseries, the artificial intelligence that has been controlling the B13 ever since Brainiac 13 originally made his deal with Lex is revealed to believe itself to be Lena Luthor. When it creates a human body (female, but bald) to pursue a romantic romantic relationship with Jimmy Olsen, Superman confronts her with the real Lena Luthor, making her realize her personality is a only computer simulation of Lena's.
Lena Luthor reappeared accompained by her grandmother, Lillian Luthor, as an adolescent. From her experience possessed by Brainiac, she still keeps a mark in her forehead.