Garneau was one of six first Canadian Astronauts and he became the first Canadian in outer space on October 5, 1984. In 1984, he was seconded to the new Canadian Astronaut Program (CAP), one of six chosen from over 4,000 applicants. He flew on the shuttle Challenger, STS-41-G from October 5 to 13, 1984, as payload specialist. He was promoted to Captain in 1986, and left the Navy in 1989, to become deputy director of the CAP. In 1992–93, he underwent further training to become a mission specialist. He worked as CAPCOM for a number of shuttle flights and was on two further flights himself: STS-77 (May 19 to 29, 1996) and STS-97 (to the ISS, November 30 to December 11, 2000). He has logged over 677 hours in space.
Garneau was appointed an Officer of the Order of Canada in 1984 in recognition of his role as the first Canadian astronaut. He was promoted the rank of Companion within the order in 2003 for his extensive work with Canada's space program.
Garneau was awarded the Key to the City of Ottawa from Marion Dewar the Mayor of Ottawa on 10 December 1984.