The Salem Female Anti-Slavery Society (SFASS) was formed on June 4, 1834, as a sister organization of the Anti-Slavery Society of Salem and Vicinity, which was formed in January 1834. Both organizations were local chapters of the American Anti-Slavery Society, which had been organized by William Lloyd Garrison in 1844. The preamble to the SFASS's constitution stated its three principles: that slavery should be immediately abolished; that people of color, enslaved or free, have a right to a home in this country and nothing should be done to discourage them from wishing to remain here; and that the society should be ready to acknowledge people of color people as friends and equals. These principles, in addition to the American Anti-Slavery Society's principles, were in direct opposition to the American Colonization Society, which had been founded in 1817, with the objective to emancipate slaves and transport them with all other free blacks to a "homeland" in Africa.

The majority of SFASS membership was comprised of wives and daughters of the members of the Anti-Slavery Society of Salem (ASSSV), who were largely from Salem's middle and professional classes. Members included Mrs. Cyrus P. Grosvenor, wife of the Baptist minister who was president of ASSSV, and Lydia L. Dodge, the daughter of William B. Dodge, a prominent educator and president of ASSSV. Lucy G. Ives, who served as SFASS vice president from1835 until 1841 and president from 1842 until 1865, was the wife of William B. Ives, the publisher of the Salem Observer, which supported abolition. Amy Redmond, who was part of Salem's prominent black Redmond, was elected vice president in 1855.

The activities of the SFASS changed throughout its 30-year existence. Early activities of the Society included distributing clothes to freed blacks in the area, supporting the National Anti-Slavery Bazaar at Faneuil Hall, organizing a sewing school for black girls, and aiding fugitive slaves in Canada. The Society supported the Liberator, an abolitionist newspaper printed by William Lloyd Garrison, by buying ten subscriptions which were donated to various organizations. They also appropriated funds to make Reverend George B. Cheever and Cyrus Grosvenor lifetime members of the New England Anti-Slavery Society. In 1835, the SFASS raised funds to support the care of a black child, Henrietta Nichols, in the Boston Samaritan Asylum. In 1837, the SFASS also held a fair on Christmas Day at which they sold items sewn by Society members.

Between 1844 and 1862, the Society organized an annual anti-slavery lecture series. The lectures were held in the fall on successive Sunday nights in either Mechanic or Lyceum Hall in Salem. Abolitionists such as Lucy Stone, Wendell Phillips, Frederick Douglass, Charles Lenox Remond, and William Lloyd Garrison, who travelled on circuit tours across the country, were requested to speak. The lecture series usually concluded each year with Garrison.

With its' primary goal, the abolition of slavery, accomplished during the Civil War, the Society voted to dissolve on January 3, 1866. It was recorded in the minutes of the final meeting that there were members who "thought that was much to be done before our country could be free from the curse of slavery, but that our work was now to be done in other ways." Some SFASS members joined the Freedman's Aid Society and similar organizations. The Society voted at its final meeting to deposit its records at the library of the Essex Institute.