The lift-off appeared to proceed as planned without major problems, judging by the commentary in an Airforce statement.
The objectives of the mission are to test guidance and navigation control, thermal protection and unmanned exit and entry, the statement said.
The space plane can stay in orbit for up to 270 days before gliding to an autonomous runway landing.
"This launch helps ensure that our warfighters will be provided the capabilities they need in the future," Andre Lovett, a launch official and vice commander of the Airforce's 45th Space Wing, said.
However, while the ultimate purpose of the X-37B and details about the craft have not been confirmed, experts said that the spacecraft was intended to speed up development of combat-support systems and weapons systems.
"Usually when the military builds a new vehicle it is for a specific purpose and always has a mission, but we don't know the exact details of this craft," Johnson-Freese said.
The launch culminated the project's long and expensive journey from Nasa to the Pentagon's research and development arm and then on to the secretive
Air Force Rapid Capabilities Office.
Officials said the X-37B would eventually return for a landing at Vandenberg Air Force Base in California, but did not say how long the inaugural mission would last.
"In all honesty, we don't know when it's coming back," Gary Payton, deputy undersecretary for Air Force space programmes, said.
Payton said the plane could stay in space for up to nine months.
Hundreds of millions of dollars have been spent on the X-37 programme, but the current total has not been released.
While space shuttles have been likened to cargo-hauling trucks, the X-37B is said to be more like a sports car, with the equivalent trunk capacity.
Unlike shuttles, it was designed for launch like a satellite, housed atop the expendable Atlas V rocket, and capable of deploying solar panels to provide electrical power in orbit.