The family relocated to Gorham, Maine, near Seargent's maternal grandfather Major George Lewis and his wife.

He graduated from Bowdoin at age 17 and began the study of law in the office of Josiah Pierce in Gorham.

[3] In 1832, he moved to Vicksburg, Mississippi and won a suit involving title to the most valuable part of the city.

[5] In July 1837, Democrats John F. H. Claiborne and Samuel J. Gholson were re-elected to the United States House of Representatives in a special election.

Writing about Prentiss's time in Congress, longtime Washington journalist Benjamin Perley Poore said that Prentiss was "the most eloquent speaker that I have ever heard":The lame and lisping boy from Maine had ripened, under the Southern sun, into a master orator.

The original, ever-varying, and beautiful imagery with which he illustrated and enforced his arguments impressed Webster, Clay, Everett, and even John Quincy Adams.

But his forte lay in arraigning his political opponents, when his oratory was "terrible as an army with banners;" nothing could stand against the energy of his look, gesture, and impassioned logic, when once he was fairly under way, in denouncing the tricks and selfish cunning of mere party management.

He reportedly rarely gave speeches from prepared notes and, instead, would ad-lib for hours to large crowds that often begged him for more.

After Mississippi repudiated her state bonds, Prentiss, who had opposed this action, moved to New Orleans in 1845.