The DJ revealed the news on her official website, where she also announced that she was expecting her second child.
"I have had the most incredible decade broadcasting on Radio 1, meeting wonderful people, helping break artists and watching live music from the world's best," she says.
Official Chart Show host Clara Amfo will be taking over the show.
"I will leave with the best memories and many great friends," said Fearne.
The 33-year-old currently presents the mid-morning show, which features regular Live Lounges from high-profile musicians.
She will present her last show on Friday 22 May, with Radio 1's Big Weekend being her last Radio 1 event.
Ben Cooper, controller of BBC Radio 1 and 1Xtra, told Newsbeat: "All of us at Radio 1 are delighted for [Fearne and Jesse] and wish them all the best for the future. It's fantastic news.
"Clara is going to be brilliant on that show.
"Her warmth, her enthusiasm, her friendliness on air. She's really slick as presenter."
Fearne is married to Jesse Wood and the couple already have a son, Rex.
"I feel extremely blessed and happy that Rex will be a big brother, and we get to welcome another Wood into the world," she wrote on her website.
"Jesse and I are very happy to announce we are having another baby. I feel extremely blessed and happy that Rex will be a big brother, and we get to welcome another Wood into the world.
"It has also been a time of big decisions and one I want to share with you now. After much time and careful thought I have decided to leave Radio 1 after ten amazing years.
"I have had the most incredible decade broadcasting on Radio 1, meeting wonderful people, helping break artists and watching live music from the world's best.
"However it is now time for a new chapter.
"I would like to thank Radio 1 for being such a great home and most of all to the listeners who have been on this journey with me. It's such a kick to know you heard a band on my show first, or that the songs I've played have helped you through the day, so thank you.
"I will leave with the best memories and many great friends.
"Here's to family and new adventures."
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Fearne Cotton is leaving BBC Radio 1 to start a "new chapter".