Thomas Pesquet and Russian cosmonaut Oleg Novitskiy are due to land in Kazakhstan at around 1410 GMT on Friday
"We confirm separation," an official at Russian Mission Control outside Moscow said of the undocking that occurred as the International Space Station (ISS) orbited above the Chinese-Mongolian border.
Pesquet and Russian cosmonaut Oleg Novitskiy are due to land in Kazakhstan at around 1410 GMT on Friday after a marathon 196-day trip that will fall just shy of a record space mission for a European Space Agency astronaut.
"It's been a fantastic adventure and amazing ride," Pesquet tweeted a few hours before the undocking.
"We got a lot of work done up here. Now it's time to come back to the planet. See you soon!"
The world was a different place when Pesquet and Novitskiy arrived at the station on November 20 for a six-month mission.
Since then, Donald Trump has replaced Barack Obama in the White House and a young centrist, Emmanuel Macron, has taken over from Francois Hollande as president in Pesquet's native France.
Novitskiy, 45, is returning to Earth with 39-year-old Pesquet, but Peggy Whitson, who accompanied them into space, will remain on the ISS until September after NASA extended her stay.
The 400-kilometre (250-mile) descent should take about three hours and 20 minutes.
Along the way, their Soyuz craft will separate into three parts, leaving the orbital and propulsion modules to burn up as they fall to Earth.
The descent module will encounter temperatures of up to 1,600 degrees Celsius (2,900 degrees Fahrenheit) as friction from the atmosphere heats its protective shield.
"Thomas has worked in a remarkable fashion," Jean-Yves Le Gall, the head of CNES, France's space agency, told AFP.
The record for the longest continuous mission in space by a European Space Agency astronaut is held by Samantha Cristoforetti of Italy, who was in orbit for 199 days from November 2014 to June 2015. She also broke the record for the longest single mission for a woman.
But that is far short of the 437-day mission by Russian cosmonaut Valery Polyakov, aboard the old Soviet-Russian space station Mir, from January 1994 to March 1995.
Pesquet underlined the fragility of Earth in an interview to AFP from the ISS.
"There are things that one understands intellectually, but which one doesn't really get," he said via video link, gently floating around in the zero gravity of space.
When it comes to global warming, "we talk of two degrees (Celsius) or four degrees -- these are numbers which sometimes exceed human understanding.
"But to see the planet as a whole... to see it for yourself... this allows you to truly appreciate the fragility."
Pesquet, France's 10th ISS astronaut, has become a social media celebrity at home with more than 550,000 followers on Twitter, where he frequently posted photographs of Earth from space.