The 374th Airlift Wing includes four groups: operations, mission support, maintenance and medical. Each group manages several squadrons in order to carry out the wing's mission.

Yokota Air Base is also home to U.S. Forces Japan, a joint service headquarters coordinating matters affecting U.S. and Japanese defense relations, and Fifth Air Force, whose mission is to enhance the U.S. deterrent posture and, if necessary, provide fighter and military airlift support for offensive air operations.

As the primary Western Pacific airlift hub for peacetime and contingency operations, the wing provides airlift for the movement of passengers, cargo and mail to all Department of Defense agencies in the Pacific area of responsibility and provides transport for people and equipment throughout the Kanto Plain and the Tokyo metropolitan area.

Yokota hosts several tenant units including the 515th Air Mobility Group, which manages air mobility operations throughout the Western Pacific, and the Japanese Air Defense Command which controls Japan's air defense mission.