The leading force behind the formation of the regiment was its first colonel, George Clark Jr., who had been an officer in the Massachusetts state militia.

"[1] Arriving in Washington, D.C. in June, the 11th Massachusetts Infantry was one of only three Massachusetts regiments to participate in the First Battle of Bull Run.

The regiment spent the early fall of 1861 helping to build fortifications around Washington.

In October, the 11th was stationed at Bud's Ferry in Indian Head, Maryland where they remained on picket duty for the winter of 1861–1862.

The 11th Massachusetts Infantry saw its first combat during the Peninsular Campaign in the spring of 1862.