He joined the French Air Force Academy of Salon-de-Provence in 1977 and was graduated as an aeronautical engineer in 1979. In 1980, he became a fighter pilot and was assigned to an operational Jaguar squadron in Istres Air Base (France). In 1985, he was assigned as a wing commander in Saint-Dizier Air Force base.
In 1988, he was graduated as a test pilot in the French test pilot school (EPNER) and was assigned to Bretigny flight test center near Paris. He then flew on different types of military and civilian aircraft including Mirage 2000, Alpha Jet, Mirage 3, Caravelle, C-160 mainly involved in radar and equipment testing.
In 1990, Léopold Eyharts was selected as an astronaut candidate by CNES (Centre National d’Études Spatiales) and assigned to support the Hermes spaceplane program managed by the Hermes Crew office in Toulouse. He became one of the test pilots in charge of the CNES parabolic flights program, an experimental aircraft (Caravelle) managed by Bretigny Flight Test Center to provide a microgravity laboratory to the scientific community. In 1992, Eyharts participated in the second European Space Agency astronaut selection. At the end of the same year, he took part in an ESA evaluation of the Russian “Buran” Space Shuttle training in Moscow, where he flew in the Tupolev 154 Buran in-flight simulator. He also participated in two additional short-duration spaceflight training courses in Star City, Moscow — six weeks in 1991 and two weeks in 1993. In 1994, he was in charge of parabolic flight testing of the Caravelle replacement, an Airbus A300 which become operational in 1995. Eyharts was assigned to full spaceflight training in January 1995. He trained as a back-up crew member for the "Cassiopeia" French-Russian space mission, which took place in August 1996.
In August 1998, Eyharts was assigned by the European Space Agency to train at NASA’s Johnson Space Center in Houston, Texas. As part of the international astronauts of the 1998 class, he attended NASA Astronaut Candidate Training which included orientation briefings and tours, numerous scientific and technical briefings, intensive instruction in Shuttle and International Space Station systems, physiological training and ground school to prepare for T-38 flight training, as well as learning water and wilderness survival techniques. He served in technical assignments until assigned to a space flight.
His first spaceflight came as part of the follow-on CNES scientific space mission named “Pégase.” He flew to the Mir Space Station in February 1998 aboard Soyuz TM-27. During the three-week Pégase mission, he performed various French experiments in the area of medical research, neuroscience, biology, fluid physics and technology. During his first space mission, he logged 20 days, 18 hours and 20 minutes in space.
He launched on board Space Shuttle mission STS-122 to the International Space Station on February 7, 2008, where he joined Expedition 16. He participated in the installation and configuration of the Columbus European laboratory module. He returned to Earth aboard mission STS-123 in March 2008.