Jacob Vernon Hamblin was born on April 2, 1819, in Salem, Ashtabula County, Ohio, to a farming family. He and his wife converted to The Church of Jesus Christ of Latter-day Saints in 1842 in Wisconsin, and migrated to Nauvoo, Illinois, the city built under the leadership of prophet Joseph Smith. When Joseph Smith was martyred in 1844, there was a crisis in succession to the leadership of the Church. Sidney Rigdon wished to be the "guardian" of the Church, but Joseph Smith had given all the keys of leadership and priesthood power to the Quorum of the Twelve Apostles led by Brigham Young, who became the second prophet of the Church. Hamblin supported Brigham Young over Sidney Rigdon. He recorded the miracle experienced by most of the Saints who were present when both Rigdon and Young spoke to the congregation:
- "On the 8th of August, 1844, I attended a general meeting of the Saints. Elder Rigdon was there, urging his claims to the presidency of the Church. His voice did not sound like the voice of the true shepherd. When he was about to call a vote of the congregation to sustain him as President of the Church, Elders Brigham Young, Parley P. Pratt and Heber C. Kimball stepped into the stand. Brigham Young remarked to the congregation: 'I will manage this voting for Elder Rigdon. He does not preside here. This child" (meaning himself) will manage this flock for a season.' The voice and gestures of the man were those of the Prophet Joseph. The people, with few exceptions, visibly saw that the mantle of the Prophet Joseph Smith had fallen upon Brigham Young. To some it seemed as though Joseph again stood before them. I arose to my feet and said to a man sitting by me, "That is the voice of the true shepherd—the chief of the Apostles" (Hamblin, Jacob. Jacob Hamblin: A Narrative of His Personal Experience, 13, 1881).
Hamblin took his family west with the body of the Saints and settled in Tooele, near Salt Lake City. He became known for his ability to create good relations with the Indians there. He felt called by God to be an emissary to the Indians. In 1854, Hamblin was called by Brigham Young to serve a mission to the southern Paiutes and settled at Santa Clara in the vicinity of the modern city of St. George, Utah. In August 1857, President Young called Hamblin to be the president of the Santa Clara Indian Mission. The Hamblin Home served as his family home from 1863 to 1868 but also as the headquarters of the mission. His wives Rachel Judd and Sarah Priscilla Leavitt accompanied him on his mission to southern Utah. At the time they moved into the home, the family included six children. Sarah bore three additional children while living in Santa Clara. Rachel passed away while the family lived there. Jacob married Louisa Bonelli in 1865. She bore one child while living in Santa Clara.
During the Utah War Hamblin spent the rest of 1857 and early 1858 shepherding non–Latter-day Saints through Utah on the trail to California and members of the Church of Jesus Christ returning to Utah from outlying settlements in order to participate in its defense should the U.S. army attack. Hamblin testified against John D. Lee attesting to Lee's involvement of the Mountain Meadows massacre.
In 1858 while in Salt Lake City, Hamblin was made a sub-Indian agent. That same year he was called on a mission to the Moquis (Hopis) of Northern Arizona. His journeys through the wilderness made him well-known as an explorer and mountain man. He was very responsive to the Spirit and obeyed it instantly. He credits the promptings of the Spirit for saving his life many times. The Hopis seemed to know he was coming through revelations of their own. They were in no hurry to change locations in order to join the Saints. They somehow knew the Latter-day Saint settlements would eventually reach their own.
- "Hamblin went home, but returned on several occasions to keep up good relations with the Hopis and the Navajos. In 1862, three Hopi men accompanied him to Salt Lake City to meet Brigham Young. In 1870 he brought a minor Hopi leader, Toova, and his wife across the Colorado River to visit the Latter-day Saint settlements in southern Utah. Tuba eventually joined the [Church of Jesus Christ], and invited the members of the Church of Jesus Christ to settle near his village of Moencopi where they founded Tuba City, named in honor of their Hopi friend." 
Hamblin was an invaluable diplomat between the Latter-day Saints and the Native Americans, surviving numerous dangerous encounters between the two. In 1870 he also acted as an adviser to John Wesley Powell before his second journey through the Grand Canyon, acting also as a translator. Hamblin said,
- "... some people call the Indians superstitious. I admit the fact, but do not think that they are more so than many who call themselves civilized. There are few people who have not received superstitious traditions from their fathers. The more intelligent part of the Indians believe in one Great Father of all; also in evil influences, and in revelation and prophecy; and in many of their religious rites and ideas, I think they are quite as consistent as the Christian sects of the day" (Hamblin, Jacob. Jacob Hamblin: A Narrative of His Personal Experience: Faith Promoting Series no. 5, 1881).
Hamblin kept a home in Kanab, Utah, and started a ranch in the House Rock Valley in the Arizona Strip at the base of the Vermillion Cliffs. Jacob Lake, Arizona on the Kaibab Plateau north of the Grand Canyon is named after him, as is Jacob Hamblin Arch in Coyote Gulch and Hamblin Wash along the US Highway 89 in Northern Arizona. He died on August 31, 1886.
The common opinion of Hamblin from his peers was that "no braver man ever lived."