Hope Hicks, the 29-year-old White House communications director, will resign in the coming weeks.
Ms Hicks joined Donald Trump's campaign in 2016, and was one of the president's longest-serving and most trusted advisers - and the last remaining member of his original inner circle of senior staff at the White House.
News of her resignation came one day after she reportedly told the House Intelligence Committee that she was occasionally required to tell "white lies" as part of her job.
But Ms Hicks had been considering leaving her post for months, according to the New York Times. She reportedly told friends she felt she had accomplished all she could in her high-level position.
In a statement, Mr Trump called the communications director "outstanding," and said she had done "great work" on his campaign and in the White House.
“She is as smart and thoughtful as they come, a truly great person," Mr Trump said. "I will miss having her by my side, but when she approached me about pursuing other opportunities, I totally understood. I am sure we will work together again in the future.”
Ms Hicks said she had "no words" to express her gratitude to Mr Trump, adding: "I wish the President and his administration the very best as he continues to lead our country."
Ms Hicks took over as the Trump administration's third communications director following the departure of Sean Spicer and the short-lived tenure of Anthony Scaramucci. Before assuming the powerful role, she served as spokesperson for the Trump campaign and a press and communications aide for the White House.
Chief of Staff John Kelly said in a statement: "When I became Chief of Staff, I quickly realised what so many have learned about Hope – she is strategic, poised and wise beyond her years ... To say that she will be missed is an understatement."
Ms Hicks has maintained a notably low profile compared to other White House aides. But her private life was plunged into the public this month as speculation grew about her relationship with Rob Porter, the former White House aide who stepped down amid allegations that he abused his ex-wives. Mr Porter has denied these allegations.
The communications director helped draft the initial White House statement defending Mr Porter, according to CNN. She was widely reported to have been in a romantic relationship with Mr Porter at the time – an entanglement that is said to have angered even Mr Trump himself.
Ms Hicks met the Trump family while working for a New York City public relations firm in 2012. Two years later, the Trump Organisation brought her onboard to handle public relations for Ivanka Trump's fashion line and a few Trump resorts.
"Hope Hicks is loved & admired by all who know her," Ms Trump tweeted. "It’s with a heavy heart, but tremendous gratitude, that I wish her well in her next steps."
Ms Hicks has not announced what job she plans to take next, and has yet to set a departure date.
Join our new commenting forum
Join thought-provoking conversations, follow other Independent readers and see their replies