"If you're in the Oval Office today, what would you say to him?" ABC News chief anchor George Stephanopoulos asked her in an exclusive interview.
"Resign," Mary Trump responded.
She said that, after being “perverted” by the family’s deep-seated “issues," her uncle was destined to become a man “utterly incapable of leading this country, and it’s dangerous to allow him to do so.”
“I saw firsthand what focusing on the wrong things, elevating the wrong people can do – the collateral damage that can be created by allowing somebody to live their lives without accountability,” she said. “And it is striking to see that continuing now on a much grander scale.”
Mary Trump recalled visiting with her uncle in the Oval Office three months after he was inaugurated.
"He already seemed very strained by the pressures ... and I just remember thinking, 'He seems tired. He seems like this is not what he signed up for,'" she said.
Tuesday’s exclusive interview with ABC News, to air on "World News Tonight With David Muir" and more on "Good Morning America" Wednesday, comes on the same day that Simon & Schuster is releasing her much-anticipated book, "Too Much and Never Enough: How My Family Created the World's Most Dangerous Man."
The book presents a scathing depiction of the sitting president, largely drawing, Mary Trump says, from the author’s own memories, conversations with family members, and legal, financial and family documents.
Mary Trump’s uncle Robert, the president’s younger brother, unsuccessfully urged a court to block the book’s release. And another legal effort by Robert Trump to block Mary Trump from publicly promoting the new book also failed, with a New York judge ruling Monday that she was free to speak publicly.
In Tuesday’s interview, Mary Trump doubled-down on the claim in her book that Donald Trump’s father – her grandfather – was a “sociopath.”
“He was incredibly driven in a way that turned other people, including his children [and] wife, into pawns to be used to his own ends,” Mary Trump said. “It’s impossible to know who Donald might have been under different circumstances and with different parents. But clearly he learned the lesson.”
According to Mary Trump’s account, tensions within the family reached a boiling point in 1999, after her grandfather died and she learned that he had essentially cut her and her brother out of his will. When she and her brother then filed a lawsuit, the rest of the family sought “to cause us more pain and make us more desperate," ending the medical insurance they had always received through their grandfather’s company, Mary Trump wrote.
They eventually reached a settlement, but on Tuesday she described the settlement as unfair.
Her own father, Fred Trump Jr., died in 1981. He was Donald Trump’s eldest brother.
The White House on Tuesday referred ABC News to its previous statements about the book. The White House previously said: "Mary Trump and her book’s publisher may claim to be acting in the public interest, but this book is clearly in the author’s own financial self-interest."
"President Trump has been in office for over three years working on behalf of the American people – why speak out now? The President describes the relationship he had with his father as warm and said his father was very good to him. He said his father was loving and not at all hard on him as a child," the statement continued.
ABC News’ Lucien Bruggeman, Nadine Shubailat and John Santucci contributed to this report.