Samuel Eli Cornish was born in Sussex County, Delaware, in 1795. Trained for the ministry at Philadelphia's African Presbyterian Church, Cornish began preaching in 1819. He was ordained in 1822 and became pastor of New York City's first African-American Presbyterian Church.

In 1827 Cornish joined with John Russwurm to establish the country's first African-American newspaper, Freedom's Journal. In 1833 Cornish joined with Arthur Tappan, Lewis Tappan, William Lloyd Garrison, and Theodore Weld to form the Anti-Slavery Society.

Cornish was a member of the executive committee of New York City's Vigilance Committee (1835-37), vice president of the American Moral Reform Society (1835-36) and editor of the Colored American (1837-39).

Some members of the Anti-Slavery Society considered the organization to be too radical. They objected to the attacks on the US Constitution and the prominent role played by women in the society. Some leaders, such as William Lloyd Garrison, Theodore Weld, Wendell Phillips and Frederick Douglass were as committed to women's rights as they were to the abolition of slavery. Others, such as Cornish, Arthur Tappan, Lewis Tappan, Gerrit Smith and James Birney disagreed with this view.

Great controversy was created when three women, Lydia Maria Child, Lucretia Mott and Maria Weston Chapman were elected to the executive committee of the Anti-Slavery Society. Lewis Tappan argued that: "To put a woman on the committee with men is contrary to the usages of civilized society."

In 1840 a group including Arthur Tappan, Lewis Tappan, James Birney, Samuel Eli Cornish and Gerrit Smith left the Anti-Slavery Society and formed a rival organization, the American and Foreign Anti-Slavery Society. This new organization refused to support the woman's rights movement and instead concentrated exclusively on the subject of slavery.

In 1846 Cornish founded the American Missionary Association and remained a executive committee member until 1855. Samuel Eli Cornish died in New York City on 6th November, 1858.