Military officials said the bomber was flying a routine test mission and that initial indications showed the crash was not survivable; investigators said determining a cause could take months.
Boeing confirmed 2 of its employees were among the dead, while officials said those aboard also included military personnel, government civilians and contractors.
The crash shut the airfield, diverted inbound aircraft and sent emergency crews to the remote site as families were being notified.
Edwards, a 480-square-mile test hub north of Los Angeles, is central to Air Force flight development, underscoring the significance of a fatal loss involving the long-serving B-52 fleet.