Rufus Anderson was born in North Yarmouth, Maine, U.S. on August 17, 1796. His father, also named Rufus Anderson, was Congregationalist pastor of the church in North Yarmouth. His mother was Hannah Parsons. He graduated from Bowdoin College in 1818, and from Andover Theological Seminary in 1822, and was ordained as a minister in 1826. He married Eliza Hill (1804–1880) on January 8, 1827. He worked at the American Board of Commissioners for Foreign Missions (ABCFM) as an assistant while studying at Andover. In 1822 he applied to go to India but was asked to remain at headquarters and later appointed assistant secretary. In 1832 he was given total responsibility for overseas work.