Merbold received a doctorate in science in 1976 from Stuttgart University and worked at the Max Planck Institute for Metals Research in Stuttgart. He specialized in both solid-state and low-temperature physics. In 1977 he was selected by ESA from among 1,800 applicants as one of three candidates for flight aboard the Spacelab-1 mission. His 1983 flight made him the first non-American to fly aboard the space shuttle. During this 11-day mission, he and his colleagues carried out 72 experiments in eight scientific disciplines.

Merbold was selected in 1988 as an ESA payload specialist for the International Microgravity Laboratory-1 Spacelab mission, which flew in January 1992. He then entered training for the first cooperative ESA-Russian mission on space station Mir. The 32-day Euromir 94 mission took place from Oct. 3 to Nov. 4, 1994.

Following his 1994 flight, Merbold continued to work with ESA. He left the European astronaut corps in 1999 and until 2004 was responsible for promoting the utilization of the International Space Station for microgravity research. He retired from ESA in 2005.