In California, the family ran a hotel and ranched in Salmon Falls, a mining town on the South Fork of the American River. Hezekiah eventually was reconciled with the Mormon Church, and the family returned to Utah in 1857. Moses, who at age fifteen had been called to serve a mission, returned to Utah in January 1858. In 1859 the Thatcher family moved to Cache Valley, where Moses helped his father locate canal and mill sites.
From 1860 to 1861 Moses studied at the University of Deseret. In 1862 he married Lettie Ann Farr. He later entered into plural marriage, marrying Lydia Ann Clayton and Georgie Snow. He had fifteen children by his three wives. In 1888 he was arrested for practicing plural marriage but was not convicted, because of a lack of evidence.
Moses mostly worked in the family businesses, which included serving as director and secretary of the Utah Northern Railroad, and as president of Thatcher Brothers Banking Company. He was also the superintendent of the Cache Valley ZCMI and organized the Cache Valley Board of Trade. He later set up similar boards throughout Utah. In 1872 he was a delegate to the Utah constitutional convention. In 1872 and 1882 he traveled to Washington, D.C., to plead for statehood before Congress, but without success.
From 1866 to 1868 he served his second mission for the LDS Church, this time to England and France. His LDS Church positions included superintendent of the Cache Valley Sunday Schools until April 1877; when the Cache Valley Stake was organized on 21 May 1877 Thatcher was ordained a high priest and set apart as stake president. He continued in this office until April 1879, at which time he was ordained an apostle for the LDS Church. Six months later he was called on a mission to Mexico.
Moses Thatcher made three trips to Mexico, not only to preach, but also to help set up colonies for Mormon polygamous refugees. The active prosecution of federal anti-polygamy laws made the prospect of Mexican colonies attractive, and Moses and his future father-in-law, Erastus Snow, were dispatched to find suitable sites. In 1887 they dedicated Colonia Juarez on a 75,000-acre tract in Corrales Basin. Mormon polygamists found refuge in Mexico until 1910, when the colonies were abandoned during the Mexican Revolution.
Thatcher is best remembered today for his difficulties with other LDS general authorities. The relationship most likely began to deteriorate when he opposed the proposal to crown LDS Church president John Taylor "prophet, priest and king."
Further problems developed over business dealings, specifically with the Bullion Beck Silver Mine in Eureka, and over his belief in the separation between church and state. In 1896 he accepted the nomination to be a Democratic senatorial candidate without the approval of church leaders. He later refused to sign a "political manifesto," which would have required him to obtain permission from the First Presidency before running for any political office. The First Presidency constantly complained of his disregard of their authority. Problems escalated and Thatcher was dropped from the Quorum of Twelve on 19 November 1896. One year later, in order to avoid excommunication, he signed a prepared statement basically stating that he was "in error." In later years he espoused socialist beliefs.
Some of the problems that Thatcher incurred were thought to be caused by his poor health. He died on 21 August 1909 and is buried in the Logan City Cemetery.