At age twenty, John D. left to find work. He worked on a steamboat and proved his trustworthiness to a merchant, a Mr. Boggs, at Galena, Illinois, where he learned more of the world and business. When he moved to Vandalia, where his sister Elizabeth lived, he became acquainted with Aggatha Ann Woolsey, whom he married 24 July 1833 after a brief courtship.

Introduced to the LDS Church, Lee and his wife moved to Far West, Missouri, in June 1838 and began the association which influenced the rest of his life. Lee and his wife were baptized on 17 June 1838 after meeting Joseph Smith for the first time. The experience of baptism was powerful enough to cause him to dedicate his life to the Mormon Church. As part of the work of building up the Kingdom of God, Lee eventually married eighteen more women and fathered sixty children. Lee became a member of the Danites, a secret fraternal order that was pledged to defend the rights of Mormons. Election day, 6 August 1838, provided Lee an opportunity to defend the rights of Mormon voters when Missourians who objected to Mormons voting started a riot. When one member of the secret order made the sign of distress, eight others, including Lee, waded in with clubs and brought calm to the street. Organized marauders on both sides set loose looting and burning; Lee later admitted to looting. Governor Lilburn Boggs sent in the state militia with his "Extermination Order" to protect the public good. The Mormons, including Lee, left Missouri for Nauvoo, Illinois.