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.
'Not leaving'
Amazon also faces increasing scrutiny from regulators, who have questioned its monopoly power. And its dominance in cloud computing is being increasingly challenged by other tech firms, such as Microsoft and Alphabet, parent company of Google and YouTube.
Mr Bezos's decision to hand over the day-to-day operation of the company came as a surprise. But investors appeared unfazed, with little change in the firm's share price in after-hours trade.
In a call with analysts to discuss the firm's financial results, Amazon chief financial officer Brian Olsavsky said: "Jeff is not leaving, he is getting a new job... The board is super active and important in Amazon's success story."
Mr Jassy, a Harvard graduate, has been with Amazon since 1997 and helped develop Amazon Web Services, which has long been seen as the profit engine of the company.
"Andy is well known inside the company and has been at Amazon almost as long as I have. He will be an outstanding leader, and he has my full confidence," Mr Bezos said.