He will become executive chairman, a move he said would give him "time and energy" to focus on his other ventures.
Mr Bezos, the world's richest man, will be replaced by Andy Jassy, who currently leads Amazon's cloud computing business.
The change will take place in the second half of 2021, the company said.
"Being the CEO of Amazon is a deep responsibility, and it's consuming. When you have a responsibility like that, it's hard to put attention on anything else," Mr Bezos said in an letter to Amazon staff on Tuesday.
"As Exec Chair I will stay engaged in important Amazon initiatives but also have the time and energy I need to focus on the Day 1 Fund, the Bezos Earth Fund, Blue Origin, The Washington Post, and my other passions."
"I've never had more energy, and this isn't about retiring. I'm super passionate about the impact I think these organizations can have," he added.
Higher public profile
Mr Bezos, 57, has led Amazon since its start as an online bookshop in 1994. The firm now employs 1.3 million people globally andhas its hand in everything from package delivery and streaming video to cloud services and advertising. He's amassed a fortune of $196.2bn, according to Forbes' list of billionaires.