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.

[9] 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.

[10][11] 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 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.

[17] The spacecraft's ground track was observed to repeat every four days, which was considered indicative for a possible imaging reconnaissance mission profile.

[17][18] 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.

James Oberg speculated that the concurrent launch of Air Force's Hypersonic Technology Vehicle HTV-2 was related to the mission.

[25] HTV-2 was launched at 23:00 UTC on 22 April 2010, i.e., 52 minutes ahead of X-37B, from Vandenberg Air Force Base in California,[26] on a suborbital trajectory supposed to last less than 25 min.