Fuller was born in Cambridge, Massachusetts. Her father, Timothy Fuller, a lawyer, gave her a vigorous classical education which was testing enough to have a lasting effect on her health. In 1836 she taught at the Temple School in Boston and from 1837 to 1839 taught in Providence, Rhode Island.
Fuller became friends with Ralph Waldo Emerson and was subsequently associated with transcendentalism. She edited the transcendentalist journal, Dial for the first two years of its existence from 1840 to 1842. When she joined Horace Greeley's New York Tribune as literary critic in 1844, she became the first female journalist to work on the staff of a major newspaper.
In the mid-1840s she organised discussion groups of women in which a variety of subjects, such as art, education and women's rights, were debated. A number of significant figures in the women's rights movement attended these "conversations". Ideas brought up in these discussions were developed in Fuller's major work, Women in the Nineteenth Century (1845), which argues for the independence of women.
She was sent to Europe by the New York Tribune as a foreign correspondent, and there interviewed many prominent writers including George Sand and Thomas Carlyle. In Italy she met the Italian revolutionary Giovanni Ossoli and had a son by him. The two supported Giuseppe Mazzini's revolution for the establishment of a Roman Republic in 1849 - he fought in the struggle while she volunteered to work in a supporting hospital.
Fuller, her husband, and her son all died when a boat transporting them back to America from Italy sank off Fire Island, New York. With them were lost Fuller's book on the history of the Roman Republic. Many of her writings were collected together by her brother Arthur as At Home and Abroad (1856) and Life Without and Life Within (1858).