It was one of the first of the Organized Reserve divisions to be called into federal service, created nearly "from scratch" after the implementation of the draft in 1940.

Previous divisions were composed of a core of either Regular Army or National Guard personnel plus draftees.

In the first years after World War I, many officers of the division were chaplains, doctors, engineers, or other men with prior military service commissioned directly from civilian life.

The division sometimes participated in Seventh Corps Area and Fourth Army command post exercises with other Regular Army, National Guard, and Organized Reserve units, but unlike the Regular and Guard units, the 88th Division did not participate in the Seventh Corps Area maneuvers and the Fourth Army maneuvers of 1937, 1940, and 1941 as an organized unit due to lack of enlisted personnel and equipment.

[5] In the United States Army's precautionary mobilization in 1940-1941 prior to the Japanese attack on Pearl Harbor, most Organized Reserve officers were ordered to active duty individually and assigned to fill vacancies in existing or newly organized Regular Army and National Guard units.

The first group of draftee fillers for the division arrived in early August, coming predominantly from New England and the Mid-Atlantic states.

Other groups, mainly from the Great Lakes and Midwest but also hailing from the Southwest and Far West, arrived in October and early November to round out the division.

One requirement for entry was that men have at least six months of service in the Army; the majority of the 88th Infantry Division's personnel did not become eligible for OCS until January 1943, around which time the Army reconsidered the troop basis, eliminating the need for many infantry officers as their future units were no longer contemplated for organization.

The 88th Infantry Division went on maneuvers in Louisiana beginning in June 1943 and was alerted for overseas movement in September, soon after completing them.

In addition, it moved overseas just as the stripping of stateside units to fill emergency requirements and provide additional sources of trained replacements became a formalized policy beginning in fall 1943, resulting in near-continuous personnel losses to many units until late summer 1944.

Destined to spend the war fighting on the Italian Front, the division arrived at Naples, Italy on 6 February 1944, and concentrated around Piedimonte d'Alife for combat training.

After being inspected by the Fifth Army commander on 5 May, the 88th Division, six days later, drove north to take Spigno, Mount Civita, Itri, Fondi, and Roccagorga, reached Anzio, 29 May, and pursued the enemy into Rome, being the first unit of the Fifth Army into the city on 4 June, two days before the Normandy landings, after a stiff engagement on the outskirts of the city.

The division went into defensive positions near Pomerance on 5 July, and launched an attack toward Volterra on the 8th, taking the town the next day.

After a period of rest and training, the 88th Division, now commanded by Major General Paul Wilkins Kendall, opened its assault on the Gothic Line on 21 September, and advanced rapidly along the Firenzuola-Imola road, taking Monte Battaglia (Casola Valsenio, RA) in the Battle of Monte Battaglia on the 28th.

Monterumici fell on the 17th after an intense artillery barrage and the Po River was crossed at Revere-Ostiglia on 24-25 April, as the 88th pursued the enemy toward the Alps.

[17] Designated TRUST (Trieste United States Troops), the command served as the front line in the Cold War from 1947 to 1954, including confrontations with Yugoslavian forces.

In October 1954 the mission ended upon the signing of the Memorandum of Understanding of London[18] establishing a temporary civil administration in the Anglo-American Zone of the Free Territory of Trieste, entrusted to the responsibility of the Italian Government.

Its mission was to command and control Army Reserve units in a six state region, which included Minnesota, Wisconsin, Illinois, Indiana, Michigan and Ohio.

The mission was changed to provide base operations support to the new 19 state region, Welcome Home Warrior ceremonies, and the Yellow Ribbon weekends.

The 88th was ordered to support Operation Allies Refuge in August 2021 as the core of Task Force McCoy.