In 1851, in response to the Fugitive Slave Law, he published the pamphlet "The Higher Law, Tried by Reason and Authority", which argued that "Injustice is the only treason; no law can legalize it, no constitution can sanction it." Readers included Ralph Waldo Emerson, who shared Spofford's antislavery principles. In 1859 Spofford became associate editor of the "Cincinnati Commercial". He was also active in Republican party politics and was a delegate to the 1856 Republican National Convention, at which John C. Frémont was nominated.