Ball was born in West Boylston, Massachusetts, studied at Phillips Academy and at Yale College for two years, then moved to South Carolina, where he tutored until entering Union College, New York, from which he graduated in 1826. The next year he married Lucy Mills, then studied theology for some years at Yale and Andover Theological Seminary. Ordained in 1831, in 1833 he became an agent of the American Home Missionary Society; working in Florida among the Negro population. In 1835 he established a successful school in Charleston, South Carolina, and also studied medicine, receiving an M.D. in 1837. While his sailing was delayed by a financial panic, he studied Chinese.
Ball arrived in Singapore in 1838 and began a lifelong pattern of teaching, preaching, publishing Chinese literature, distributing tracts, and doing medical work, with evangelism always his first concern. In 1841 he moved to Macao for the sake of his wife's health, and in 1844 to Hong Kong, where she died. Ball then moved to Canton and in 1846 married Isabella Robertson, a missionary from Scotland. While running a boys' school and supervising the publication of books and tracts, including a popular Almanac, he devoted much of his energy to touring with his medicines and tracts. After furlough from 1854 to 1857, with his health impaired, he spent most of his final years doing tract distribution from his street chapel in Canton, where he died.