Elizabeth was born on 3 February 1821 in a house on Dicksons Street in Bristol, England, to Samuel Blackwell, a sugar refiner, and his wife Hannah (Lane) Blackwell. She had two older siblings, Anna and Marian, and would eventually have six younger siblings: Samuel (married Antoinette Brown), Henry (married Lucy Stone), Emily (third woman in the U.S. to get a medical degree), Sarah Ellen (a writer), John and George. Four maiden aunts, Barbara, Ann, Lucy and Mary, also lived with Blackwell during Blackwell's childhood.

The Blackwells' financial situation was unfortunate. Pressed by financial need, the sisters Anna, Marian and Elizabeth started a school, The Cincinnati English and French Academy for Young Ladies, which provided instruction in most, if not all, subjects and charged for tuition and room and board. The school was not terribly innovative in its education methods - it was merely a source of income for the Blackwell sisters. Blackwell's abolition work took a back seat during these years, most likely due to the academy.  Blackwell converted to Episcopalianism, probably due to her sister Anna's influence, in December 1838, becoming an active member of St. Paul's Episcopal Church. However, William Henry Channing's arrival in 1839 to Cincinnati changed her mind. Channing, a charismatic Unitarian minister, introduced the ideas of transcendentalism to Blackwell, who started attending the Unitarian Church. A conservative backlash from the Cincinnati community ensued, and as a result, the academy lost many pupils and was abandoned in 1842. Blackwell began teaching private pupils.  Channing's arrival renewed Blackwell's interests in education and reform. She worked at intellectual self-improvement: studying art, attending various lectures, writing short stories and attending various religious services in all denominations (Quaker, Millerite, Jewish). In the early 1840s, she began to articulate thoughts about women's rights in her diaries and letters and participated in the Harrison political campaign of 1840.  In 1844, with the help of her sister Anna, Blackwell procured a teaching job that paid $400 per year in Henderson, Kentucky. Although she was pleased with her class, she found the accommodations and schoolhouse lacking. What disturbed her most was that this was her first real encounter with the realities of slavery. "Kind as the people were to me personally, the sense of justice was continually outraged; and at the end of the first term of engagement I resigned the situation." She returned to Cincinnati only half a year later, resolved to find a more stimulating way to spend her life.

Did she ever receive any recognition?