The officials had submitted their resignations before Trump's inauguration on January 20 as is required of officials holding posts appointed by the president.
At least four senior US State Department officials are leaving their posts by Friday after the Trump administration accepted their resignations from presidentially appointed positions, a senior department official said.
Resignations and turnovers among senior leadership during a presidential transition is common.
Political appointees chosen by the president and confirmed by the Senate were obliged, as usual, after Trump's Nov. 8 election victory, to submit letters of resignation to give the new president the opportunity to name his own people to the jobs.
Turnover is the rule, rather than the exception, among the top officials in the US government when the White House changes hands from one party to another, in this case from Democrat Barack Obama to Republican Donald Trump.
TRT World's Simon Marks has more details.
At least one media report suggested that the departures amounted to a mass resignation, but several US officials said this was not the case.
"Of the officers whose resignations were accepted, some will continue in the Foreign Service in other positions and others will retire by choice or because they have exceeded the time limits of their grade in service," acting State Department spokesman Mark Toner said in a statement.
US President Donald Trump's nominee for Secretary of State, former Exxon Mobil Corp chairman Rex Tillerson, was approved by the Senate foreign relations committee. Tillerson, who has yet to be confirmed by the full Senate, will be under some pressure to fill these senior positions.