YouTube CEO Susan Wojcicki is leaving the role after nine years.
The technology executive has spent almost 25 years at parent company Google and was their 16th employee.
In a blog post, Wojcicki announced her decision "to start a new chapter focused on my family, health and personal projects I'm passionate about".
Neal Mohan, YouTube's chief product officer, will take over as head of the video platform.
"The time is right for me, and I feel able to do this because we have an incredible leadership team in place at YouTube," said Wojcicki, who will continue to work at YouTube in the short term to help with the transition.
In her post, she singled out Mohan's work launching YouTube TV, as well as leading YouTube Music, Shorts and Premium.
YouTube has improved its relationship with the music industry in recent years, following long-term concerns about the so-called value gap in terms of revenue shared with rights-holders from user-generated content.
Last year, YouTube revealed that $6 billion was paid to the music industry over 12 months, making it one of the biggest global partners.
As well as launching subscription tier YouTube Music in 2018 in the UK, it supports industry initiatives such as MMF Accelerator and the BRITs.
Susan Wojcicki will have an advisory role across Google and Alphabet.
"This will allow me to call on my different experiences over the years to offer counsel and guidance across Google and the portfolio of Alphabet companies," she said.