The Reaper was assigned to the 49th Wing. No other aircraft were involved in the mishap, which occurred at about 8:30 a.m. local time, the release said.
Emergency response teams responded to the scene, and an investigation is under way, the base said.
The 49th Wing is part of Air Education and Training Command, and trains airmen to pilot MQ-9s and F-16 Fighting Falcons, as well as be sensor operators for Reapers.
An F-16 also crashed at Holloman on July 13. Its pilot successfully ejected, sustaining minor injuries.
Stephen Losey covers leadership and personnel issues as the senior reporter for Air Force Times. He comes from an Air Force family, and his investigative reports have won awards from the Society of Professional Journalists. He has traveled to the Middle East to cover Air Force operations against the Islamic State.