Tinker AFB began in the USA's buildup to World War Two. In October of 1940s, a group of Oklahoma businessmen conceived a plan to make land near Oklahoma City available to the US Army. This was achieved, and construction for a new air materiel depot, the Midwest Air Depot, began June of 1941. Construction was not to be complete until March of 1942, and the staff of the new base took up offices in Oklahoma City in January of 1942 to prepare for action in the new war. Shortly before the depot was opened, an announcement was made that a new Douglas Aircraft Assembly Plant would be constructed next to the depot. The Midwest Air Depot opened on schedule. In June 1942 General "Hap" Arnold, US Army, announced that the new field would be renamed Tinker Field, to honor Oklahoma native, Osage tribe member, Major General Clarence L. Tinker, who was killed in action on the last day of the Battle of Midway, June 7 1942.

Tinker Field promptly got to work repairing and modifying a variety of large airplanes of the war, including B-17, B-24, and B-29s, C-47 and C-54 cargo planes, overhauled engines, and received the C-47 Skytrains and variants, and the A-20 Havocs, produced at the Douglas plant. In all, many thousands of aircraft moved through Tinker before war's end.

After the war Tinker Field continued in a reduced capacity, and contributed maintenance to the aircraft of the Berlin Airlift. The Douglas assembly plant was acquired by the War Department for Tinker's use and the Field was upgraded to Base. Through the Cold War, Tinker continued maintaining and revising aircraft of all types, notably the B-29 Superfortress, B-47 Stratojet, and C-97 Stratofreighter, and their replacements, and their replacements' replacements.

One March 25th 1948 Tinker AFB was the site of the world's first successful tornado prediction, three hours before a tornado landed on the base. Five days earlier, a tornado had struck with no prediction, and caused millions of dollars of damage; this time the personnel, planes, and equipment were moved into shelter, possibly saving many lives and much more damage.

In 1957 Buddy Holly and The Crickets performed at Tinker AFB, recording four songs, "An Empty Cup", "Rock Me My Baby", "You've Got Love", and "Maybe Baby" at the Tinker Officer's Club.

Since 1977 Tinker AFB has been the home base for the 552nd Air Control Wing, flying the E-3 Sentry AWACS carrier, a critical early warning aircraft in airspace defense. Tinker also houses an air refueling wing and other support units and facilities.