Animation from the Defense Advanced Research Projects Agency shows the Falcon Hypersonic Technology Vehicle-2 launch.
The unmanned glider was developed for the U.S. military to respond to threats at 20 times the speed of sound or greater.
It's part of a program to develop technology that can respond to threats anywhere in the world in just an hour.
The problem occurred during the critical point of transition to aerodynamic flight, DARPA said in a statement.
The 7:45 a.m. launch from Vandenberg Air Force Base, 130 miles northwest of Los Angeles, was the second of two planned flights of a Falcon Hypersonic Technology Vehicle-2. Contact was also lost during the first mission.
Defense analyst John Pike of Globalsecurity.org wasn't surprised with the latest failure because the hypersonic test flight program is still in its infancy.
"At this early stage of the game, if they did not experience failures, it's because they're not trying very hard," he said.
Pike said it's possible for engineers to still glean useful information about what worked and what didn't, despite the flight ending prematurely. The key is to analyze what happened in the final five seconds before contact was lost.
The Associated Press contributed to this report.