He was selected as an astronaut in 1998 and assigned to the Space Station Operations Branch of NASA's Astronaut Office. He became a Russian liaison for the Space Station Operations Branch, working in Moscow, then served as a crew support astronaut for the second and fourth resident crews of the International Space Station (ISS). In 2002 he became a CapCom (spacecraft communicator) in the Mission Control Center in Houston, Texas. In October 2007, Wheelock flew to the ISS aboard space shuttle Discovery, which delivered the Node 2 module. He flew again to the ISS aboard a Soyuz spacecraft in June 2010, where he took command. He has accumulated more than 178 days in space.