Lucretia was born in Nantucket, Massachusetts to Quaker parents. During her lifetime she worked tirelessly for human equality. She learned about slavery at an early age and took up the cause for the abolition of slavery. She and her husband, James Mott, aided fugitive slaves who made their way north through the Underground Railroad. She became an active member of the American Anti-Slavery Society, but when she was excluded as a delegate to the 1840 World Anti-Slavery Convention in London because she was a woman, she soon became involved with women's rights. This led to her joining Elizabeth Cady Stanton in organizing the Seneca Falls Women's Rights Convention in 1848. She also served as president of the American Equal Rights Association from 1866-1869 and wrote the book Discourse on Woman in 1850.
In July, 1848, Lucretia and Elizabeth organized the First Woman's Rights Convention, although she still continued to work for the abolition of slavery. In 1866 she became the first president of the American Equal Rights Association, an organization with the main purpose of achieving equality for both African Americans and women.
In addition to her causes, she and her husband, James Mott, also helped to found Swarthmore College in 1864.