The facility which houses Yokota Air Base was originally constructed by the Imperial Japanese Army (IJA) in 1940 as Tama Airfield, and used as a flight test center.

Tama was first identified by United States Army Air Forces (USAAF) in November 1944 by a 3rd Reconnaissance Squadron F-13 Superfortress photo-reconnaissance aircraft, flying from Tinian in the Mariana Islands.

The name was to have been changed to Wilkins Army Air Base (WAAB) after Medal of Honor recipient Raymond "Ray" Wilkins, but orders for this never arrived and it remained under the name Yokota Army Airfield until the USAAF became the USAF in 1947, at which point it became Yokota Air Base.

The initial USAAF use for the base was for airlift operations when the 2d Combat Cargo Group arrived with four C-47 Skytrain squadrons.

Defense budget restrictions in the late 1950s caused several PACAF wings based in Japan to be reassigned or inactivated.

Yokota was used for ferrying B-52 Stratofortresses to Southeast Asia along with being a base for US-based deployed F-105 Thunderchief 35th, 36th and 80th Tactical Fighter Squadrons.

[4]: 264  The 475th had no numbered flying squadrons, but operated a few T-39 Saberliners and UH-1 helicopters, along with supporting transient MAC cargo and passenger aircraft.

The Tokyo Metropolitan Government has advocated opening Yokota to civilian flights as a method of relieving traffic at Haneda and Narita Airport.

"[8] Personnel and aircraft from the base assisted with Operation Tomodachi following and during the March 2011 Tōhoku earthquake and tsunami and Fukushima I nuclear accidents.

RQ-4B Global Hawks of Detachment 1, 319th Operations Group deploy to Yokota from Andersen AFB in Guam during the typhoon season, normally between June and December.

[18] The newly renovated Air Mobility Command (AMC) Passenger Terminal is on the main part of the base next to the flightline.

It is a 5 to 7-minute walk from the Kanto Lodge (see below) and offers Space-Available flights to various destinations in PACAF such as Alaska, Guam, Hawaii, Korea, Okinawa, Singapore, as well as the Continental United States.

Gravel used in the construction of the airfields was taken from the Tama River, lowering the riverbed and affecting the traditional irrigation system (Fuchū-yōsui), which had provided water to local communities since the early Edo period.

The base also caused great stress to nearby inhabitants in a number of other ways, such as fuel leaks and spills that contaminated groundwater and well water, foul odors and fires, deafening noise pollution, and repeated plane crashes.

The 374th Force Support Squadron is responsible for providing an enhanced quality of life, facilities and programs for 11,000 military, civilian and dependents as well as 150,000 transient personnel per year.

[24] Each year in May, Yokota Air Base opens the gates to the Japanese community for its annual Friendship Festival.

Each year, service member volunteers base-wide form "D Squadron" for the event, offering some visitors an enhanced on-base experience.

On the May 22, the 46th President of the United States, Joe Biden, visited Japan with the arrival of related equipment, including the dedicated Air Force One, but the Friendship Festival was held as scheduled.

[25] The Department of Defense Education Activity operates schools at Yokota for children of personnel assigned to the base.

[26] Higher educational opportunities for those in the military and working for the Department of Defense, as well as for family members at Yokota are available through several contracted academic institutions.

The base is also the birthplace of US Marine Captain, former UFC fighter and Fox Sports analyst Brian Stann.