Questions have long been raised about whether Thornton, 54, who was picked for the post by former secretary of state Rex Tillerson, would be replaced under his successor, Mike Pompeo. Her appointment had been opposed by former White House chief strategist Steve Bannon.
"Acting Assistant Secretary of State for East Asian and Pacific Affairs Susan Thornton has announced her intention to retire from the Foreign Service at the end of July," State Department spokeswoman Heather Nauert said in a statement.
"We are grateful for her service of over two and a half decades to the Department of State, including numerous challenging assignments around the world," Nauert added.
Nauert did not say when Pompeo planned to announce a replacement, but said: "He is moving forward with efforts to nominate candidates for leadership roles across the department, including for this key position."
Thornton's retirement comes as President Donald Trump's administration prepares for negotiations to ensure Pyongyang abandons its nuclear weapons, following a summit between Trump and North Korean leader Kim Jong-un in Singapore.
Pompeo, who is charged by Trump with leading follow-on negotiations, said the US hoped to achieve "major disarmament" by North Korea within the next two and half years.
Thornton's departure also comes amid trade tensions between Washington and Beijing at a time when the two countries are trying to cooperate on North Korea.
Thornton could not be immediately reached for comment on Saturday.