Lucretia Mott began her public work through teaching and Quaker ministry. Recognized as a minister in 1821, she traveled to preach and made opposition to slavery an important part of her religious message. She followed Elias Hicks during the Quaker division of 1827, emphasizing individual conscience and the spiritual capacity of every person. With her husband James she refused goods produced by enslaved labor, connecting abolitionist principles to everyday purchasing decisions.

In 1833 she helped organize the Philadelphia Female Anti-Slavery Society, which brought Black and white women into a common campaign. The society petitioned, raised funds, and supported antislavery lectures and publications. Mott's willingness to speak before mixed audiences challenged prevailing restrictions on women's public activity. She continued despite threats and mob violence: Pennsylvania Hall, where an antislavery convention was meeting, was burned in 1838. Her household also assisted people escaping enslavement through the Underground Railroad.

Selected as a delegate to the World Anti-Slavery Convention in London in 1840, Mott was excluded from full participation because she was a woman. Her encounter there with Elizabeth Cady Stanton helped connect the antislavery struggle with demands for women's rights. In July 1848 she joined Stanton, Martha Coffin Wright, Mary Ann M'Clintock, and Jane Hunt in organizing the Seneca Falls Convention. The meeting adopted the Declaration of Sentiments, challenging women's legal and political subordination and calling for voting rights.

Mott's Discourse on Woman, delivered in 1849 and published in 1850, disputed claims that women were naturally inferior and argued that restricted education and opportunity created apparent differences. Her reform commitments extended to peace, religious freedom, and educational access. She supported institutions that widened opportunities for women and participated in the founding circle of Swarthmore College.

After emancipation she continued to seek equal citizenship. In 1866 she became the first president of the American Equal Rights Association, supporting suffrage for African Americans and women. As disagreements over the Fifteenth Amendment divided reformers, she sought cooperation between competing women's suffrage organizations. Active into old age, she died in 1880, leaving a career that linked religious conscience with sustained collective action against slavery and unequal rights.