Padelford was a Unitarian and an ardent abolitionist with ties to the New England Emigrant Aid Company, which armed and organized settlers who took part in the "Bleeding Kansas" conflict.

In 1860, he was nominated as the Republican Party candidate for Governor of Rhode Island.

Anti-war Republicans and textile interests joined Democrats to back the young William Sprague IV, the nephew of former Rhode Island Governor and Senator William Sprague III.

Sprague, running as a "Conservative" against Padelford's "Radical" candidacy, won the election by a margin of 12,278 to 10,740 votes, with twice the customary turnout at the polls.

[1] After the American Civil War began in 1861, Padelford won two consecutive elections for Lieutenant Governor, serving from 1863 to 1865.