The first woman in America to be ordained and the first to officiate at a marriage was born in a log cabin, on the family farm near Rochester, New York. At an early age Antoinette determined to become a minister. With money saved from teaching, she graduated from Oberlin College and was allowed—despite being a woman—to study theology, but she was not allowed to graduate.

She then lectured on women's rights, temperance, and antislavery issues. Thomas Wentworth Higginson and Theodore Parker invited her to preach in their Unitarian churches.

In 1856 Antoinette Brown was ordained and installed in the Congregational Church in South Butler, New York. Upon marrying abolitionist and suffragist Samuel Blackwell, she became a Unitarian and helped to found All Souls Unitarian Church in Elizabeth, New Jersey, later being elected minister emeritus.

At the World's Congress of Religion she declared, "Women have become indispensable to the religious evolution of the human race."

Oberlin College awarded her the degree of Docotor of Divinity. She died in 1921 at the age of ninety-six.