In 1830 Ross was among the major donors and founders of Oakland College, a Presbyterian-affiliated school for young men near Rodney, Mississippi, which operated from 1830 to 1870.

It ordered the sale of his plantation to generate revenue to fund the transport of the freed slaves to Mississippi-in-Africa, the state's colony in West Africa that eventually became part of Liberia.

[1] In the American Revolutionary War of 1775–1783, Ross rose to the rank of Captain of the Second Dragoons under the leadership of General Thomas Sumter (1734–1832).

[4] In the 1830s, together with Chamberlain and three other planters, Edward McGehee, Stephen Duncan, and John Ker, Ross co-founded the Mississippi Colonization Society.

These major slaveholders believed that free blacks threatened the stability of American society, and that transporting freed slaves to Africa might be a long-term solution.

[5][6] The will stipulated that those slaves who chose not to emigrate to Africa should be sold to the highest bidder, with the proceeds invested to go to the American Colonization Society to build a new university in Liberia for the colonists and support it for 100 years.

They expressed considerable opposition to the program of the American Colonization Society, but thousands of free blacks did migrate as pioneers to Liberia.

During this period, they worked under the authority of Isaac Ross Wade at Prospect Hill Plantation, with the stipulation that they were technically free and would be paid for their time.

[5] Finally traveling from Natchez, Mississippi by ship, the Prospect Hill freedmen reached Liberia in two groups in 1848.

[5] In Mississippi in Africa: The Saga of the Slaves of Prospect Hill Plantation and Their Legacy in Liberia Today (revised edition, 2010), author Alan Huffman argues that tensions introduced by the development of this colony (and the larger influence of Americo-Liberians in the country) created longstanding resentments among the indigenous tribesmen.

Because the Americo-Liberians dominated the country politically and economically into the 20th century, suppressing the native tribes, there was great resentment against them among the indigenous peoples.