Jassy worked for 5 years after graduation before doing his MBA. He worked as a project manager for a collectibles company, MBI, and then he and an MBI colleague started a company and closed it down.
He joined Amazon in 1997, with several other Harvard MBA colleagues. His early roles included marketing manager.
In 2003, he and Jeff Bezos came up with the idea to create the cloud computing platform that would become known as Amazon Web Services (AWS), which launched in 2006. Jassy headed AWS and its team of 57 people.
In March 2016, Jassy was named Person of the Year by the Financial Times, and a month later in April, Jassy was promoted from senior vice president to CEO of AWS. That year Jassy earned $36.6 million.
In April 2017, Jassy criticized rival Oracle's database business, claiming that "it has been a lonely place for customers" due to their high prices and vendor lock-in.
In 2020, for his work as CEO of AWS, Jassy earned a base compensation of $175,000, plus a restricted stock unit award of 4,023 shares (a value of $12,104,844.93 as of July 26, 2020) of Amazon with vesting beginning in 2023. He also received a restricted stock unit award in April 2018 for 10,000 shares (a value of $30,089,100 as of July 26, 2020), which vest 37.5% in 2021, 12.5% in 2022, 37.5% in 2023, and 12.5% in 2024.
On February 2, 2021, it was announced that Jassy will succeed Jeff Bezos as the CEO of Amazon sometime in the third quarter of 2021, with Bezos transitioning to executive chairman.This will take effect on July 5, 2021. 
Outside of his roles at Amazon, Jassy is also the chairman of Rainier Prep, a charter school in Seattle.
They live in the Capitol Hill neighborhood of Seattle, in a 10,000-square-foot house bought in 2009 for $3.1 million. In October 2020, it was reported that Jassy had bought a $6.7 million 5,500-square-foot house in Santa Monica, California.