May was born and raised in Boston, Massachusetts in 1788. (? 1797 ?) When he was four years old his six year old brother Edward died while they were at play in their barn. May claimed that the loss of his brother and the dreams he had following the fatal accident led him to devote his life to God and inspired his passion to "rectify the world's wrongs." He started attending Harvard in 1813 at the age of fifteen; during his junior year he chose to become a minister. In addition, while he was at Harvard and afterwards, he taught school in Concord, Massachusetts. During this time, he met many prominent Unitarians and activists including Noah Worcester, who instilled in May the idea of peaceful opposition. He was in a party that was one of the first to travel on the Crawford Path, opened in 1819 by Abel and Ethan Crawford as a route to the summit of Mount Washington, New Hampshire and today considered to be the oldest White Mountains trail in continuous use.
May graduated from Harvard Divinity School in 1820 and became a Unitarian minister. Following his graduation, he considered preaching in New York City and Richmond, Virginia prior to accepting a position in Brooklyn, Connecticut as the only Unitarian minister in that state. Here, he came to the forefront of the Unitarian movement and became well known throughout New England as he attempted to establish Unitarian churches and reform.
May began a biweekly publication, The Liberal Christian, in January 1823; its main goal was to explain the Unitarian Theology. He helped in the formation of Windham County Peace Society in 1826; in 1827, May organized a statewide convention for school reform in Connecticut, and he started a series of lectures in 1828. Meanwhile, he also belonged to the American Colonization Society whose purpose was to send the slaves back to Africa. May’s belief in perfectionism through imitating the life of Jesus Christ strongly influenced his involvement in reform movements. A pacifist, he actively participated in establishing peace societies, speaking out against the death penalty, and advocating nonresistance. He practiced this last belief to the extent of rejecting self-defense. He became a leader in the temperance movement, believing it to be a form of abolitionism since he saw men as slaves to drink. He was perhaps most renowned for his work in education reform as he sought to improve facilities, teachers, and curriculum in public elementary schools. May believed schools should be racially integrated and coeducational, and he advocated the philosophy of Swiss theorist Johann Pestalozzi. He spent time tutoring his sister Abigail May in philosophy and the humanities and wrote in a letter to her, "What you say relative to the need for universal education is certainly true. Nothing is of unimportance in the formation of the mind."
In 1830, May happened to meet and create a strong friendship with William Lloyd Garrison, which pushed him into the abolitionist movement. Although his abolitionist views alienated his family, friends, and other clergymen, he remained true to his beliefs. He helped Garrison found the New England Anti-Slavery Society, the American Anti-Slavery Society, and the New England Non-Resistance Society, in addition to working for the Massachusetts Anti-Slavery Society. He served as one of the writers for the constitutions of some of these societies, and as a lecturer and general agent for the New England Anti-Slavery Society. Fighting for racial equality and better schools, May defended Prudence Crandall in the 1830s as residents of Canterbury, Connecticut fought her decision to close the school she ran for white girls and open it solely to young black ladies. This experience caused him to abandon his support for the colonization movement. May was one of the delegates from Massachusetts who went to the World Anti-Slavery Convention in London in 1840.
May became pastor of the Unitarian Church of the Messiah of Syracuse, New York in 1845, serving until 1868. He fought the Fugitive Slave Law of the 1850s by making announcements during his sermons of fugitive slaves in the area and took collections on their behalf, as well as aiding escaped slaves along the Underground Railroad. As a prominent abolitionist in the city, May, with the help of many Liberty Party members, including Gerrit Smith and Samuel Ringgold Ward, planned and successfully executed the rescue of Jerry McHenry, a man arrested as a fugitive slave, from the police. In addition to fighting for the abolition of slavery, he fought for the equality of free blacks in his congregations by allowing them to sit in the front as opposed to the segregated rear pews. This act resulted in his reproach by white congregation members and also in his quitting some of his parishes. These actions, particularly late in the 1850s and immediately after President Lincoln was elected in 1860, led abolitionism’s opponents to violently attack May as well as burn him in effigy.