Smith is commonly regarded as the first Latter Day Saint missionary following the organization of the Church of Christ by his brother, Joseph.

One of the Eight Witnesses to the Book of Mormon's golden plates, Samuel Smith remained devoted to his church throughout his life.

When Smith's father missed a mortgage payment on the family farm on the outskirts of Manchester Township, near Palmyra, a local Quaker named Lemuel Durfee purchased the land and allowed the Smiths to continue to live there in exchange for Samuel's labor at Durfee's store.

At the end of June 1829, Samuel, along with his brother Hyrum, his father, and several men of the Peter Whitmer Sr. family, signed a joint statement declaring their testimony of the golden plates that Joseph Smith said he translated into the Book of Mormon.

[7] In July 1832, Smith and Hyde went to Providence, Rhode Island; they baptized two people, but in response to threats of violence left the state after being there only twelve days.

[4] When the first high council of the church—at the time the chief judicial and legislative body of the church—was organized on February 17, 1834, Smith was one of twelve men chosen as a member.

At the Battle of Crooked River, Smith fought next to apostle David W. Patten, who subsequently died from wounds received in the skirmish.

As a result of the conflict, the Latter Day Saints were expelled from Missouri and Smith moved with the main body to their new headquarters in Nauvoo, Illinois.

Due to his role in the Battle of Crooked River, Smith fled Missouri almost immediately, along with Lorenzo D. Young, Benjamin L. Clapp and Charles C. Rich.

Samuel was attacked by mobbers, while traveling toward Carthage after hearing rumors of trouble, and is said to have developed some kind of stitch in his side evading them, which may have contributed to his subsequent death.