Hope Hicks, the White House communications director and one of President Trump's longest-serving advisers, is to step down, the administration says.
The 29-year-old former model and ex-Trump Organization employee has been by Mr Trump's side for years.
She is reported to have told colleagues she felt she had accomplished all she could in the White House.
She is the fourth person to serve as White House communications chief.
White House spokeswoman Sarah Sanders said it remained unclear when Ms Hicks would leave the administration.
She said her resignation was not connected to testimony she gave to the House Intelligence Committee on Tuesday.
Ms Hicks is reported to have admitted to the panel that she had occasionally told what amounted to "white lies" for President Trump.
But she denied lying about anything relevant to the investigation into alleged Russian meddling in the 2016 election, US media reported.
Trump 'understood'
During the election campaign, Ms Hicks served as press secretary. She took over as the head of the White House communications team last August, after the abrupt firing of Anthony Scaramucci.
Before him, Sean Spicer and Mike Dubke both served in the role - which involves overseeing a busy press department.
But Ms Hicks has kept a remarkably low profile in the job.
"Hope is outstanding and has done great work for the last three years. She is as smart and thoughtful as they come, a truly great person," Mr Trump said in a statement.
"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."
Out of the White House but likely not the spotlight
Analysis by the BBC's Anthony Zurcher in Washington
Hope Hicks had been there since the beginning; since before the beginning. When the Trump campaign was just a ragtag band of political neophytes, she was the one distributing press releases and answering media requests.
Where others had stumbled or been pushed out of Donald Trump's orbit, Hicks quietly persevered - and rode the train all the way to one of the most powerful White House jobs.
Now she too is gone. She lasted nearly as long as the preceding three White House communications directors combined, but the position continues to be cursed.
Administration sources insist that it was a planned exit, that she was simply waiting for the right time. It's hard, however, to imagine timing worse than this. It comes just a day after her eight hours of testimony before a congressional committee investigating possible Trump campaign ties to Russia, where she reportedly admitted to telling "white lies" in defence of the president.
Although she may be exiting the White House, it's unlikely she escapes the spotlight so easily. She had a ringside seat to many of the controversies that have swirled around the Trump campaign and presidency - and subsequent revelations could put her name in the headlines again.
Ms Hicks is seen as a key witness in the ongoing inquiry into whether the Trump team colluded with Russia.
During the nine-hour hearing on Tuesday, she reportedly stonewalled lawmakers about a 2016 meeting between members of the Trump campaign and a Russian lawyer at Trump Tower.
Democratic Senator Richard Blumenthal, a member of the powerful Senate Judiciary Committee investigating Russian meddling, said that she now needed to testify.
"She has no right to claim executive privilege. She has no claim to refuse to come before the judiciary committee now she's stepped down. She should be a witness before the judiciary committee," he said.
Earlier this month her actions were scrutinised amid a scandal involving White House staff secretary Rob Porter, who quit amid domestic abuse allegations. She was, at the time, reported to have been dating Mr Porter.
Ms Hicks helped draft an initial statement defending Mr Porter and her handling of the controversy reportedly displeased Mr Trump.
Who is Hope Hicks?
- Brought up in Greenwich, Connecticut, and was a talented lacrosse player at high school and college
- Took up modelling as a teenager and once appeared in an ad for Ralph Lauren
- Previously worked for a public relations company that handled Ivanka Trump's fashion business and the Trump Organization's property brand
- Joined the Trump Organization in 2014 and Donald Trump brought her on to his campaign team a year later, despite her lack of political experience
- Nicknamed "Hopester" by Mr Trump, she is said to be one of his most trusted aides and among the few who could challenge him to change his views