He was founding president of the Presbyterian-affiliated Oakland College, near Rodney, Mississippi, serving from 1830 to his death in 1851.

Known to favor abolition of slavery, he was a co-founder with major planters of the Mississippi Colonization Society.

Affiliated with the American Colonization Society, it was formed to relocate free people of color from the state to West Africa, in the colony that developed as Liberia.

[2] To improve the situation, Chamberlain negotiated for the control of the college to be relinquished by the state to the Presbyterian Church, which was effected in 1824.

The state legislature established Alcorn University there, the first black land grant institution in the country.

[1] In the 1830s, together with planters Isaac Ross (1760–1838), Edward McGehee (1786–1880), Stephen Duncan (1787–1867), and John Ker (1789–1850), he was a member of the Mississippi Colonization Society, an auxiliary of the American Colonization Society whose goal was to send free people of color and freed slaves to their colony in West Africa known as Mississippi-in-Africa.

[7] They had four daughters: On September 5, 1851, Chamberlain was stabbed to death by George A. Briscoe, a pro-slavery planter, after he spoke out against the "peculiar institution.

[7] In 1879, the Chamberlain-Hunt Academy in Port Gibson, Mississippi, was named after him and David Hunt (1779–1861), a millionaire planter and philanthropist.