Wojcicki has led YouTube for the past nine years, previously she worked for YouTube's parent company Google for more than two decades.
According to reports Wojcicki told employees that working for YouTube had been “exhilarating, meaningful and all-consuming.”
She said she will be focusing on her personal life, health and other projects.
Wojcicki was part of the team that worked on products such as Google Image Search, Google’s first Video, Book search and AdSense.
Her resignation means there will currently be no female CEO in Big Tech.