A tone of independence and moral zeal pervaded Susan's childhood home, dominated by her father, Daniel, a Quaker Abolitionist and cotton manufacturer. Her father instilled in his children the ideas of self-reliance, self-discipline, and self-worth. Since Quakers stressed a moral life, both her parents were strong supporters of the abolitionist and the temperance movements. After the family moved from Massachusetts to Battensville, N.Y., in 1826, she attended a district school, then a school set up by her father, and finally a boarding school near Philadelphia.

Susan began teaching at the age of 17. In 1849 she settled in her family home, now near Rochester, N.Y. and began her first public crusade, on behalf of temperance. Discouraged by the limited role that women were allowed in the established temperance movement, Susan helped found the Woman's State Temperance Society of New York, one of the first organizations of its kind. She began writing temperance articles for the "Lily", the first woman-owned newspaper in the United States. Through the paper's editor, Amelia Bloomer, she met women involved in the Abolitionist movement and in the recently formed women's suffrage movement. In 1852 she met Elizabeth Cady Stanton and joined her in the campaign for women's rights, even for a time donning the "bloomer" costume of skirt and loose trousers as a sign of protest against the restrictiveness of women's clothing. After 1854 she devoted herself with vigor and determination to the antislavery movement, serving from 1856 to the outbreak of the Civil Was as an agent for the American Anti-Slavery Society.