He has logged 1 601 hours in space and more than 19 hours of space walks during seven shuttle flights. These include the Atlantis mission to deploy the Galileo spacecraft (October 1989), the Discovery flight (June 1998) that made the final docking with the Russian space station Mir, and the Endeavour flight (June 2002) to the International Space Station during which he took three space walks to install the Canadian Mobile Base System. He was selected as an astronaut in 1980 and retired from the corps in July 2005.

Chang-Diaz was a visiting scientist at the Massachusetts Institute of Technology from 1983 to 1993, leading a programme to develop plasma propulsion technology for future crewed missions to the planet Mars.