Mr Perrottet, 41, had also served as Treasurer, Minister for Industrial Relations and Minister for Finance, Services and Property in the former coalition government.
"I love NSW," he said in a statement on Friday.
"It has been an absolute honour to represent the eight million people who call this great state home, especially as their 46th premier."
Mr Perrottet is moving to the United States for a global role as BHP's US head of corporate and external relations.
At age 39, Mr Perrottet became the youngest premier in the state's history after Gladys Berejiklian resigned in October 2021.
He served for almost 18 months, coming into the role as the state emerged from months of COVID-19 lockdowns, before Labor took office at the March 2023 election.
Mr Perrottet, who is giving up his lower house seat of Epping, has previously been touted as a possible Liberal candidate for a seat in federal parliament.
"I got into politics to promote ideas and new ways of thinking and I am proud to have been part of a government that left NSW in a much better place than we found it," Mr Perrottet said.
His departure sets the scene for NSW Liberal party to face two by-elections, after Hornsby MP Matt Kean announced his resignation in June.
Mr Kean was treasurer in Mr Perrottet's government.
Dominic Perrottet with his family during a campaign rally for the 2023 state election. (Jane Dempster/AAP PHOTOS)
Mr Perrottet plans to give his valedictory speech when state parliament returns in August, before formally resigning on August 11.
Opposition Leader Mark Speakman said Mr Perrottet had left an indelible mark on NSW.
"He was a reformer who had a passion for new ideas and imagination for what would make NSW a better place for all," he said.
Mr Perrottet's five budgets delivered strong surpluses and record infrastructure investment, driving the state's asset recycling program and establishing the NSW Generations Fund, valued at more than $17 billion.
"His legacy is one of remarkable achievements and steadfast leadership," Mr Speakman added.