The regiment was mustered again into federal service on 30 March 1917 for World War I. Soldiers from the 6th Massachusetts were transferred to form the regiments of the 26th "Yankee" Division. The majority of the soldiers helped form the 104th Infantry Regiment. After the deployment of the Yankee Division the remaining soldiers of the 6th Mass. (15 officers and 279 enlisted men) trained at Camp Wadsworth and formed the 4th Pioneer Infantry Regiment, commanded by Colonel Holton B. Perkins and filled to wartime strength with draftees. The pioneer regiments included such specialists as mechanics, carpenters, farriers and masons. They were supposed to work under the direction of the engineers to build roads, bridges, gun emplacements and camps "within the sound of the guns." They received standard infantry training so that they could defend themselves, but there are very few documented instances of any pioneer troops unslinging their rifles. Once in France, the regiment was selected to be re-trained to form the 382nd Infantry Regiment. Before that transition could be executed the Fall Offensives of 1918 pushed the 4th Pioneer Infantry into service as engineer support and labor troops. The regiment was demobilized in February 1919 at Camp A.P. Hill, VA. Served in the following campaigns: Battle of Saint Mihiel, Meuse Argonne Offensive, and Battle of Lorraine 1918.