Leaving camp on March 17, 1862, the regiment took part in the siege of Yorktown and the battles of Williamsburg and Fair Oaks. In the latter engagement, the troops fought like veterans, holding their position unsupported until nearly surrounded. Three companies were on special duty at the opening of the action and, being unable to reach the regiment in its exposed position, fought with the 57th Pennsylvania Infantry. After a month spent on picket duty, the 105th was again in action at Glendale and Malvern Hill, and, by the time it reached Harrison's Landing, the ranks were so reduced by wounds and sickness that less than 100 men were fit for active duty.