Prada's brand CEO Gianfranco D'Attis will leave the Italian luxury firm at the end of the month by "mutual agreement", Prada said on Sunday.
Prada Group's CEO Andrea Guerra will take on the role of brand CEO on an interim basis, the company told Reuters.
The news was first reported by fashion trade publication WWD.
Luxury fashion has seen several changes in senior leadership and creative directors.
Luxury goods giant Kering, which owns Gucci, last week named Renault boss Luca de Meo as its new CEO, replacing Francois-Henri Pinault, who has led the heavily indebted family firm since 2005.
Top luxury houses are also betting on a new design direction to help rekindle interest from shoppers, who have pulled back on fashion as prices rise.
Earlier in June, LVMH-owned Dior appointed its menswear designer, Jonathan Anderson, to also head womenswear designs and haute couture, replacing Maria Grazia Chiuri.
Kering in May appointed former Valentino designer Pierpaolo Piccioli as creative director of Balenciaga, replacing Demna, who was taking up the chief design job at Gucci.
Designer changes have also taken place at Chanel, Versace, Valentino and LVMH-owned Celine among others.