[4] Pesquet returned to space in April 2021 on board the SpaceX Crew Dragon for a second six-month stay on the ISS.

Pesquet is a black belt in judo and lists basketball, jogging, swimming and squash as his favourite sports.

He spent his final year before graduation at the École Polytechnique de Montréal, Canada, as an exchange student on the Aeronautics and Space Master.

From October 2001, Pesquet worked as a spacecraft dynamics engineer on remote sensing missions for GMV, S.A. in Madrid, Spain.

On 10 June 2014, NASA announced that Pesquet would serve as an aquanaut aboard the Aquarius underwater laboratory during the NEEMO 18 undersea exploration mission, which began on 21 July 2014 and lasted nine days.

[12] He was also the backup to ESA astronaut Andreas Mogensen who flew to the International Space Station on a 10-day flight in September 2015.

In 2023, Pesquet participated in the ESA PANGAEA training organized by the European Space Agency, held between Italy (Bletterbach canyon), Germany (Noerdlingen-Ries crater) and Spain (Lanzarote Island)[13][14][15][16] together with the colleagues Takuya Onishi and Jessica Wittner.

Arriving at the ISS on November 19, 2016, he was the first French astronaut since Léopold Eyharts helped install the Columbus European laboratory module during Expedition 16.

Expedition 50 Commander Kimbrough and Pesquet disconnected cables and electrical connections on PMA-3 to prepare for its robotic move on March 26, 2017.

The two spacewalkers lubricated the latching end effector on the Canadarm2 robotic arm, inspected a radiator valve suspected of a small ammonia leak and replaced cameras on the Japanese segment of the outpost.

[20] On June 2, 2017, MS-03 undocked from the ISS, carrying Pesquet and Novitskiy back to Earth, concluding a 196-day mission in space.

[21] On 11 March 2020, ESA announced in a blog post that Pesquet would return to the ISS in the second half of 2021 for a second six-month stay, in which he would become the first European astronaut to launch on board an American Commercial Crew Vehicle.

The first three EVAs were conducted with Shane Kimbrough on the 16, 20, and 25 of June with the tasks to install the first two Roll Out Solar Arrays (iROSA) on the station.

[33] On 12 April 2021, Thomas Pesquet was nominated Goodwill Ambassador for the Food and Agriculture Organization of the United Nations.