Ms Conway, who was the American leader’s campaign manager during the 2016 election race, was the first woman to successfully steer a White House bid before becoming a senior counsellor to the president.
She informed Mr Trump of her decision in the Oval Office.
Ms Conway cited a need to spend time with her four children in a resignation letter she posted on Sunday night.
I’m Leaving the White House. Gratefully & Humbly.
Here is my statement:https://t.co/MpYxVfrY2N
God Bless You All.
— Kellyanne Conway (@KellyannePolls) August 24, 2020
Her husband, George, had become an outspoken Trump critic.
Ms Conway wrote: “We disagree about plenty but we are united on what matters most: the kids.
“For now, and for my beloved children, it will be less drama, more mama.”
She is still slated to speak at the Republican National Convention this week.
Her husband, a lawyer who renounced Mr Trump after the 2016 campaign, had become a member of the Lincoln Project, an outside group of Republicans devoted to defeating Mr Trump.
The politically adversarial marriage generated much speculation in the Beltway and online. George Conway also announced on Sunday that he was taking a leave of absence from both Twitter and the Lincoln Project.
Kellyanne Conway worked for years as a Republican pollster and operative and originally supported senator Ted Cruz in the 2016 Republican primary.
She moved over to the Trump campaign and that August became campaign manager as Stephen Bannon became campaign chairman.
Bannon was indicted two days ago for fraud.
Ms Conway cited a need to help her children’s remote learning during the coronavirus pandemic as a need to step away from her position.
She had remained a trusted voice within the West Wing and spearheaded several initiatives, including on combating opioid abuse.
The adviser was also known for her robust defence of the president in media appearances, at times delivering dizzying rebuttals, and once extolled the virtues of “alternative facts” to support her case.
Ms Conway was also an informal adviser to the president’s re-election effort, but resisted moving over to the campaign.
Her departure comes at an inopportune time for Mr Trump, who faces a deficit in the polls as the Republican National Convention begins on Monday.
Her exit was first reported by The Washington Post.