He served as the 24th governor of Ohio and as U.S. Postmaster General in the Cabinet of President Abraham Lincoln during the American Civil War.

Before the outbreak of the American Civil War, he refused the demands of Kentucky and Virginia state authorities for the extradition of fugitive slaves or the punishment of those who helped them.

He denounced secession and Ohio's "Copperheads", established a consistent supply of arms and equipment for the new troops, and was a vocal supporter of Lincoln's policies.

However, errors by the Governor and his subordinates led the state's alliance of Republicans and War Democrats to drop Dennison as a candidate in 1862.

Historian Richard H. Abbott wrote, "No Ohio chief executive [before Dennison] had ever exercised such powers and fulfilled such duties with a greater sense of public responsibility and determination.

Dennison accepted this turn of events with good grace, capably advised his successor, and provided valuable services in helping recruit black troops for Ohio units.

Of Dennison's single term in the opening stages of the Civil War, historian John S. Stilt wrote, "His wisdom and foresight were appreciated by few and condemned by many....

Camp #1 of the Department of Ohio of the Sons of Union Veterans of the Civil War is named for Governor William Dennison.

Dennison is honored with a full-size bronze depiction inside the Cuyahoga County Soldiers' and Sailors' Monument in Cleveland, Ohio for his service as governor during the Civil War.

[3] Camp Dennison is a census-designated place (CDP) just outside Indian Hill in southern Symmes Township, Hamilton County, Ohio, United States.