The site of Dyess AFB was originally Abilene Army Air Base, then popularly called Tye Airfield, and was constructed and opened in 1942 as a flying training center for cadets and for reconnaissance and fighter-bomber groups, and housed the 474th Base Headquarters and Airbase Squadron. At the end of the war the redesignated Abilene AAF was inactivated, and assigned to Continental Air Command; it was used for Texas Army National Guard training for a few years.

The Cold War created a new demand for defense facilities, and Abilene Field was reactivated as Dyess Air Force Base after a three year reconstruction project, renamed in honor of the late Lt. Col. William E. Dyess, a Medal of Honor recipient with a remarkable career as an Army Air Force commander, infantry commander, and survivor of the Bataan Death March. Dyess AFBs first unit was the 341st Bombardment Wing, the first of several bomber units housed here. Dyess was a significant first strike response base, with SAC units on constant rotating ready alert. In the late 1950s and through the mid-1960s Dyess was also home to Atlas missile silos, until these were decommissioned due to technology advances. In the 1980s Dyess took a leading role in bomber training and bombardment and airlift mission capability.

Since the end of the Cold War, Dyess' units have consolidated and remain active in armed service in airlift and bomb strike missions in Europe and the Persian Gulf, Operations Iraqi Freedom and Enduring Freedom.

In the early 2000s, Dyess converted its main sources of base power to wind energy and biomass, making the base one of the greenest bases in the armed forces, and helping the US Air Force become less dependent on limited and foreign fuels.