Born in 2303, O'Donnell lived at the Omicron Theta colony. She met Doctor Noonian Soong on the colony, and the two fell in love. However, her mother disapproved of their relationship due to the age gap, so they met in secret. They boarded the SS Wisconsin in 2328 to get married in secret on Mavala IV. Though they had no biological children, she considered each of the Soong-type androids like children.
O'Donnell assisted Soong in his work on artificial lifeforms, and helped create the android Data, as well as his four predecessors, including Lore and B-4. When creating Data, Juliana was responsible for giving Data the capability to later play music and paint, as well as other creative outlets, feeling that he deserved a chance to express himself even if he lacked the emotional capacity to explore that side of himself.
When the Crystalline Entity attacked the colony in 2338, the Soongs fled the planet, leaving Data and his "brother", Lore, behind. The two made their way to the Terlina system; however, Juliana was seriously injured in the attack, and fell into a coma.
In a last attempt to preserve her memory, Soong built a new android, one indistinguishable from a Human, and transferred his wife's memories into it, using a synaptic scanning technique. Following Juliana's death, Soong activated the android, who remained unaware of her new state of being. (TNG: "Inheritance")