With her stepping down, YouTube's chief product officer, Neal Mohan, will be the new head of YouTube, she said.
Announcing her decision, Wojcicki, 54, said she will focus on "family, health, and personal projects I'm passionate about."
She served previously as a senior vice president for ad products at Google, and became CEO of YouTube in 2014.
She was among Google's earliest employees and has been with the parent company Alphabet Inc for nearly 25 years.