She is named after Lex's foster sister who had been killed by their foster father, Casey Griggs. After Lena's birth, Lex takes advantage of Contessa Erica's wish to be unconscious at child birth by keeping her permanently drugged and unconscious at his corporate headquarters, not wishing to share his daughter's love with anyone else (Although he himself avoids attending the birth to provide himself with a clear alibi for an assassination attempt he arranged at the time).
When Brainiac 13 arrives from the 64th century, the modern Brainiac possesses the infant Lena to escape being deleted by his future self. Even after Brainiac leaves Lena's body, Luthor trades her to Braniac 13 for control of the future technology that has transformed Metropolis.
Lena returns to visit Lex Luthor during the Our Worlds at War crossover, where she has apparently been aged to adolescence by Brainiac 13. Lena plays a sneaky role during the event, helping Luthor and his allies beat Imperiex by feeding her father information, while secretly manipulating events to benefit Brainiac 13. She is ultimately convinced at the end to side with her father. At the end of the crossover, Brainiac 13 and Imperiex are both destroyed, and Lena is regressed to infanthood and returned to 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 shown as still having Brainiac discs on her forehead.
In the Superman's Metropolis miniseries the artificial intelligence controlling the B-13 technology believes itself to be Lena Luthor. When it creates a human body (female, but bald) to pursue a romantic relationship with Jimmy Olsen, Superman confronts her with the real Lena Luthor, making her realize her personality is a computer simulation of Lena's.
Lena was not seen after Lex Luthor lost the presidency.