The regiment served in this manner until the spring of 1864, when it was assembled to participate in Brigadier General Alfred Sully's Northwestern Indian Expedition against the Sioux.

From there, the regiment marched toward the Canada–United States border in search of "hostile" Sioux, but returned to Fort Union empty handed.

The two separated parts of the regiment moved south, but the detachment that had gone to rescue the immigrant train arrived in Nashville first, due to traveling via a steamboat down the Missouri River.

In December, 1864 the 8th Minnesota participated in the Third Battle of Murfreesboro, Tennessee, where it suffered 13 men killed and 77 wounded.

The Regiment was present for General Johnston's surrender to U.S. Gen. Sherman at Bennett Place, Durham, North Carolina.