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.

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