The couple shared the news in a statement on Instagram, saying how they made the decision after "many meaningful and difficult conversations".
Since their wedding in 2005, Trudeau and Grégoire have remained fixtures in Canadian public life. The couple have three children together.
Long before their relationship though, Grégoire was childhood friends with Trudeau's late brother, Michel.
Watch: Justin Trudeau on feminism and fatherhood. Post continues below.
"We could play Tarzan for hours," she told Maclean's about her friendship with the youngest Trudeau brother.
In 1998, Michel was killed in an avalanche in British Columbia.
He was only 23 and his body was never recovered.
The Trudeau family eventually called off the recovery search and built a chalet nearby as a memorial for him.
The Canadian Prime Minister has written about the moment he was told his brother had died.
"Michel had been doing what he loved most when he died, backcountry skiing with friends. I felt a spasm of guilt. What was Michel doing out on that glacier? Why hadn't I, as his older brother, found some way to protect him?" he wrote in his 2014 memoir.