In 1852 Pratt was the first to announce publicly that the church practiced plural marriage. Shortly afterwards he was sent to Washington, D.C., to publish The Seer to respond to criticisms of controversial Mormon doctrines. Pratt's theological speculations eventually made LDS Church president Brigham Young uneasy. The two men disagreed at first privately, then openly. Several times Pratt was ordered to recant his beliefs, which he did, only to resume teaching them again.

In 1856 Pratt presided over the Mormon Church in Britain again. Four years later he was called to the eastern United States. The following year, he moved to southern Utah to oversee development of a church-sponsored cotton industry. In 1864 he accepted a call to preside over the church's Central European mission.

Throughout the period from the 1850s to the 1870s when he was in Utah Pratt was a delegate to constitutional conventions and served in the territorial legislature as a member and later speaker of the house of representatives. He also prepared new editions of the Book of Mormon and other Mormon scriptures.