Murray, 28, said he had "learnt a lot" from Mauresmo but they had "mutually agreed" to end their partnership.
"Dedicating enough time along with the travel has been a challenge," twice Grand Slam champion Mauresmo added.
Since he began working with her in June 2014, Murray has won seven titles - including his first two on clay - but has failed to add to his two majors.
In a joint statement, Murray added: "She's been a calming influence in the team and we will all miss having her around.
"I'll take some time to consider the next steps and how we progress from here, but I'd like to thank her for everything she has done. She's been an invaluable member of the team."
Frenchwoman Mauresmo, 36, added: "Working with Andy over the last two years has been a fantastic experience for me.
"I've thoroughly enjoyed being part of the great team of people he has around him. I wish him and the team well and I hope he goes on to win many more titles."
Murray - who lost his number two ranking to Roger Federer after his defeat by Novak Djokovic in the Mutua Madrid Open final on Sunday - was previously coached by former world number one Ivan Lendl.
Under Lendl he won the 2012 US Open and 2013 Wimbledon.