USA-212 was the first flight of the Boeing X-37B Orbital Test Vehicle 1 (X-37B OTV-1), an American robotic vertical-takeoff, horizontal-landing (VTHL) spaceplane. It was launched aboard an Atlas V rocket from Cape Canaveral on 22 April 2010, and operated in low Earth orbit. Its designation is part of the USA series.

The spaceplane was operated by Air Force Space Command, which has not revealed the specific identity of the spaceship's payload for the mission. The Air Force has stated only that the spacecraft would "demonstrate various experiments and allow satellite sensors, subsystems, components, and associated technology to be transported into space and back."

USA-212 was launched on an Atlas V 501 rocket, tail number AV-012, from Space Launch Complex 41 at the Cape Canaveral Air Force Station in Florida. The launch, which was conducted by United Launch Alliance, occurred at 23:52 UTC on 22 April 2010, placing the spacecraft into low Earth orbit for testing.

The X-37B spacecraft was originally intended to be deployed from the payload bay of a NASA Space Shuttle, but following the Columbia accident, it was transferred to a Delta II 7920. It was subsequently transferred to the Atlas V following concerns over the X-37B's aerodynamic properties during launch.

The launch was the first flight of the Atlas V 501 configuration, and the first in four years to use a 5.4-meter (18 ft) payload fairing. Prior to the installation of the spacecraft, the Atlas rocket was moved to the launch pad and performed a wet dress rehearsal on 2 April 2010. It was returned to the Vertical Integration Facility the next day for final assembly. The X-37 arrived at the VIF on 8 April. On 9 April, a 24-hour delay was announced. It subsequently slipped a further 24 hours after the landing of Space Shuttle Discovery on Mission STS-131 was delayed, as the Eastern Range could not have been reconfigured quickly enough to accommodate both events on the same day. After a series of delays, it was set for 19 April 2010. On 21 April, the Atlas was rolled back out to the launch pad for launch. The launch window on 22 April opened at 23:52 UTC, and closed at 00:01 on 23 April.

Most of the mission parameters for the USA-212 flight have not been disclosed. The vehicle is capable of being on-orbit for up to 270 days. The Air Force stated the mission time would depend on progress of the craft's experiments during orbit. Mission control was handled by the 3rd Space Experimentation Squadron, 21st Space Wing, of the Air Force Space Command in Colorado Springs.

In May 2010, an amateur astronomer claimed to spot the spacecraft from his home in Toronto, Ontario, Canada. Shortly after the initial observation, several more detailed observations were made by amateur skywatchers from around the world, who reported the spacecraft to have an almost circular 401 to 422 km (249 to 262 mi) low Earth orbit with an inclination of 40°. The group believed in their calculations and observations with a high degree of confidence. The spacecraft's ground track was observed to repeat every four days, which was considered indicative for a possible imaging reconnaissance mission profile.

For two weeks, starting on 29 July, the amateur skywatchers were unable to find the spacecraft in the locations they had predicted, leading them to believe it had suddenly changed its course. During the mission, the vehicle was observed to change its orbit multiple times, with a total delta-v of the first four orbit changes amounting to 102 m/s (330 ft/s). A common characteristic of all the orbits was that the ground track nearly repeated every few days. By 12 November 2010, the orbit had been lowered to 281 by 292 km (175 by 181 mi) with the ground track now repeating every three days (47 orbits).