Jim Mattis, Defence Secretary - 20 December 2018
The departure, scheduled for February, was announced in an evening tweet by the president.
In his social media post, Mr Trump said General Mattis would retire "with distinction" at the end of February, but did not name a successor.
A distinguished former Marine Corps general, Gen Mattis had held the post since Mr Trump took office.
Why did he leave?
The move came just one day after the president controversially announced the withdrawal of US troops from Syria.
Although not referring directly to that, in his resignation letter Gen Mattis said the president had the right to have a defence secretary "whose views are better aligned" with his.
The two had diverging public views on a number of subjects, including Mr Trump's decision to withdraw from the Iran nuclear deal.