As the host wing for Scott AFB, its mission it to enable the numerous Team Scott missions through infrastructure and communications support platforms, as well as provide programs and facilities for the welfare of the men and women and their families who serve here.

The wing's operational mission is to provide unrivaled air mobility operations through its fleet of C-21 aircraft and through its Total Force Integration partnerships with the Guard and Reserve in flying KC-135 and C-40 aircraft.
 

The wing owns 14 C-21As, that operate at Scott Air Force Base. The wing provides maintainers and aircrews for the KC-135 and C-40 missions who work alongside Guard and Reserve personnel, who also have operation control of the aircraft and the missions.

The wing also maintains responsibility for the 375th Aeromedical Evacuation Training Squadron at Wright-Patterson Air Force Base, Ohio, which is responsible for all AES qualification training on behalf of the Air Force.

Together, the wing provides senior leader airlift for senior leaders and flies aeromedical evacuation missions for wounded warriors and medical patients, and provides the nation with air refueling capabilities.

The wing's mission is also to develop and care for Airmen and their families while fostering base and community partnerships.

The 375th AMW is comprised of several staff agencies and four groups: the 375th Medical Group, 375th Operations Group, 375th Mission Support Group and 375th Communications Group, totaling approximately 2,900 active-duty personnel who perform those missions.