He was born to Noah Porter Jr. (1781–1866) (one of the first ministers of First Church of Christ, Congregational in Farmington, Connecticut) and his wife, born Mehitable Meigs, in Farmington, Connecticut on December 14, 1811. His younger sister was Sarah Porter, founder of Miss Porter's School, a college preparatory school for girls. He graduated in 1831 from Yale College, where he was a member of the Linonian Society. On April 13, 1836, in New Haven, he married Mary Taylor, daughter of Nathaniel Taylor (who presided over the creation of the Yale Divinity School and created what came to be known as "New Haven theology") and his wife Rebecca Marie Hine. They had several children, and two daughters survived them.
He was ordained as a Congregational minister in New Milford, Connecticut from 1836 to 1843. He served as pastor at a Congregational Church in Springfield, Massachusetts from 1843 to 1846. He was elected professor of moral philosophy and metaphysics at Yale in 1846.
Porter was inaugurated as President of Yale College on Wednesday, October 11, 1871. He continued to serve as head of the college until 1886.
Influenced by the German refugee writer and philosopher Francis Lieber, Porter opposed slavery and integrated an antislavery position with religious liberalism.