Barksdale Air Force Base is named in honor of Lt. Eugene Hoy Barksdale, Air Corps, U.S. Army, who lost his life Aug. 11, 1926 , while flight testing a Douglas O-2 observation airplane over McCook Field, in Dayton, Ohio. Originally Barksdale Field, construction began in 1933 for what would for a time be the world's largest airfield, 22,000 acres for training and practice. Soon the 20th Pursuit Group and 3rd Attack Wing arrived to take advantage of the large base area.

Before World War Two, Barksdale was already adapting to new air projection tactics and strategies developing in Europe and Asia. The pursuit and attack wings were replaced with fighter and light bomber units, and a new Air Corps flying school was created. In May 1940 Barksdale hosted "complete military maneuvers," what would today be considered practice war maneuvers, reflecting combat as it was being fought in Europe. During World War Two, Barksdale Field was a crucial training center for pursuit pilots and especially bomber crews, as well as housing and training Free French Air Force units and Nationalist Chinese aircrew.

In the Cold War Barksdale was reassigned to Strategic Air Command and became Headquarters Second Air Force. Barksdale remained a training center, and various reconnaissance and bombardment units over the next several decades, generally on constant watch or ready alert against enemy first strike.

Since the Cold War Barksdale ABF has provided fueling and basing missions to targets around the world, in operations including Operations Just Cause, Desert Shield, Desert Storm, and Desert Fox, as well as vital bombardment sorties in several confrontations and conflicts in the 1990s. The first bombing sortie against Iraq in Desert Storm, involving seven B52Gs, was launched from Barksdale, in the longest combat sortie to that time.

In the 21st Century, Barksdale served as President George Bush's secure shelter during the 911 attacks, and was the nexus of many missions in Iraq and Afghanistan in Operations Enduring Freedom and Iraqi Freedom.