The TV presenter has hosted the BBC Two show since 2011, taking over from original host Claudia Winkleman.
In a post on Instagram, Zoe explained why she was leaving the show after a decade.
"Dance lovers, after 10 joyous years I am waltzing away from It Takes Two," she wrote.
Zoe told her followers: "As a massive @bbcstrictly fan I have loved spending my Autumn teatimes with the celebrity dancers, the gorgeous & awesome pro dancers, the judges, my girl Vicky Gill, Rylan, Gethin & of course my main man Ian Waite.
"Time now for some new cha cha challenges. I will continue to support the Strictly family on the Breakfast Show & can’t wait to watch the Class Of 2021 from my sofa."
She added: "Huge love & grateful thanks to Tess & Claude & the whole Strictly clan, the ITT fans, my Glam Squad, Eve Winstanley, Alex McLeod, the BBC2 gang, & of course the best telly crew ever.
"I will miss you all immensely. As Iveta would say 'Friends for the life'."
Broadcaster Zoe had fronted the show after competing in Strictly herself in 2005 where she finished in third place.
Meanwhile former Stirctly professional Ian Waite has also announced he will no longer be a part of the spin-off.
Ian, who regularly appeared to analyse the celebs in training, said: "It is with great sadness but also a lot of pride that after 10 years presenting Waites Warm Up on #ItTakesTwo the sister show to @bbcstrictly I will be putting away my wand to focus on my dance fitness brand Fitsteps and also my up and coming tour with Vincent Simone The Ballroom Boys.
"I want to thank all the amazing crew, make up artists, directors, producers, who made it so enjoyable to come in to work."
Taking over for Zoe is former pro dancer Janette Manrara who co-hosts alongside Rylan.
It Takes Two airs weeknights Monday-Fridays and feature interviews with contestants and creative team as well as backstage content.
Strictly Come Dancing continues on Saturday and Sanday nights, hosted by Tess Daly and Claudia Winkleman.
Picture: Zoe Ball - (C) BBC - Photographer: Ray Burmiston