In 1855, Denison was convinced by his brother-in-law, Isaac Goodnow, that he should move to Kansas Territory to help establish a new town for the New England Emigrant Aid Company.

On March 13, 1855, Denison joined a party of Company members leaving Boston, and made his way to Kansas Territory, which was soon to boil over with violence.

In April 1857, at a meeting of the Methodist Church Conference, a plan for the college was properly inaugurated.

During his term, Denison managed a number of important accomplishments, including establishing a faculty and acquiring valuable land that would later become the center of the university.

He held this position from 1874 to 1879, before retiring to work with the Methodist church in the town he helped settle, Manhattan.