On this test flight, the X-37B will deploy a set of solar panels designed to keep it powered for as long as 270 days. Its other activities are secret.
The Air Force isn't saying when the flight will end, but the space plane is supposed to land on a runway at Vandenberg Air Force Base in California.
Some critics fear the 29-foot-long craft could someday carry weapons to shoot down enemy satellites.
The X-37B was built by Boeing in Seal Beach. It began as a technology demonstrator for NASA but was taken over by the Air Force in 2006.
The Pentagon will have to determine whether it is worth the huge expense to develop this experimental space plane for military use.