After the assassination of Joseph Smith, anti-Mormon sentiment continued to grow in western Illinois. Anti-Mormon mobs didn't dare attack Nauvoo, but they began to raid smaller, outlying Mormon settlements. Though Governor Ford resisted pressures to attempt a formal expulsion, he told Mormon leaders that the only resolution to the problem would be for the Mormons to leave the state.

Brigham Young, who had won the allegiance of a majority of the Nauvoo Saints, began making plans to do just that. While the Saints made preparations to leave, they continued work on the temple, believing it necessary to receive their "endowments" in the House of the Lord before abandoning Nauvoo. Work on the temple was completed in the winter of 1845, and the first major emigration from Nauvoo began in February 1846. After reaching Council Bluffs (Kanesville), Iowa later that year, they made camp in order to prepare for the long trek to Utah.

While the Saints were camped at Council Bluffs, Captain James Allen of the United States Army West arrived to enlist 500 Mormons to fight in the Mexican War, which had broken out earlier that year. The Saints were not eager to support the U.S. in a war from which they stood to benefit little, especially given that the U.S. had done nothing to protect them from the Missouri and Illinois mobs. Furthermore, they were hesitant to send 500 men into war when manpower would soon be desperately needed for the great trek westward. But Brigham Young realized that the poverty-stricken Saints desperately needed whatever income they could get to assist with the westward migration, and with his encouragement the "Mormon Battalion" was formed. The battalion never saw an actual battle, but made the longest infantry march in military history, 2,000 miles from Council Bluffs, Iowa to San Diego, California.

After the majority of the Saints had departed Nauvoo, leaving only the most impoverished or those such as Emma Smith who refused to follow Brigham Young, Nauvoo was sacked and occupied by an anti-Mormon mob.

In 1847, Brigham Young and the other Saints left Council Bluffs and made the "Great Trek" to the Salt Lake Valley in Utah. Immigrating Saints and other travellers for points west continued to walk or ride the "Mormon trail" to Utah for approximately two decades, until the transcontinental railroad was finally completed in 1869.