The passage of the Kansas-Nebraska Act of 1854 focused the slavery struggle on Kansas. When President Franklin Pierce signed the bill with its provision for "popular sovereignty" for the territories, Pomeroy allegedly told the president, "Your victory is but an adjournment of the question from the halls of legislation at Washington to the open prairies of the freedom-loving West, and there, sir, we shall beat you" (William E. Connelley, A Standard History of Kansas and Kansans
, p. 1219). Pomeroy became one of the organizers of the New England Emigrant Aid Company, which funneled more than $100,000 through Pomeroy, as its financial agent, to aid settlers who favored Kansas as a state free from slavery.
Accompanying a group of sponsored settlers, Pomeroy first located in Lawrence, Kansas Territory, in 1854. As chairman of the defense committee, he failed to protect Lawrence from the proslavery raiding party of 21 May 1856, but the "Sack of Lawrence" became the cause célèbre at the first national Republican presidential nominating convention in Philadelphia in 1856, where Pomeroy made a fiery speech, condemning the South. Pomeroy was a leader of the Territorial Kansas independent Free State party, which evolved into the Republican party by 1859.
Ordered by the Emigrant Aid Society to establish a Free State town in northeast Kansas, Pomeroy purchased land in and near Atchison, previously a proslavery stronghold. He also purchased control of an influential proslavery newspaper, Squatter Sovereign, which was quickly renamed Freedom's Champion.