The regiment was assigned to Major General John G. Foster's Department of North Carolina, later designated as the XVIII Corps.

While based in New Bern, North Carolina, the 51st Massachusetts took part in several expeditions involving numerous units from Foster's command and were engaged in the Battle of Kinston, the Battle of White Hall and the Battle of Goldsborough Bridge, among other engagements.

The Fifty-first Regiment was organized at Worcester September 25 to October 30, 1862,[1] during which time Thomas Wentworth Higginson became a captain in the unit.

[2] November 25–30, the unit moved to Boston, and from there to New Bern, North Carolina.

[1] Records show that no members of the 51st were killed in battle, but 44 enlisted men died of disease in the nine months service.