The man fired by Mr Trump last year told ABC News: “I don’t buy this stuff about him being mentally incompetent or early stages of dementia.”
“I don’t think he’s medically unfit to be president. I think he’s morally unfit to be president,” he added.
The President lashed out at Mr Comey, calling him a “slimeball” in a series of tweets before the US TV interview and labelling him the “WORST FBI director in history, by far”.
He said Mr Comey was lying and is “not smart”.
The former FBI chief appeared to hold nothing back when he got in front of the cameras.
Slippery James Comey, a man who always ends up badly and out of whack (he is not smart!), will go down as the WORST FBI Director in history, by far!
— Donald J. Trump (@realDonaldTrump) April 15, 2018
“[He] talks about and treats women like they’re pieces of meat [and] lies constantly about matters big and small,” said Mr Comey.
He also said it was “stunning” to think that Russia could have compromising information on the President, but that he could not discount the possibility.
Mr Comey has kept quiet about his time under Mr Trump for nearly a year, with the interview and his new book, A Higher loyalty, breaking the silence.
The former lawyer also compares the President to one of the mafia bosses he once fought to prosecute, calling his leadership “ego driven and about personal loyalty”.
Mr Comey was sacked in May 2017, with officials accusing him of mishandling the investigation into Hillary Clinton’s use of email.
Many Democrats blame his decision to reopen the probe – 11 days before the 2016 election – for Mrs Clinton’s shock defeat.
In the interview, Mr Comey said he assumed Mrs Clinton would win.
He told ABC: “I don’t remember spelling it out, but it had to have been, that she’s going to be elected president and if I hide this from the American people, she’ll be illegitimate the moment she’s elected, the moment this comes out.”
Opponents of the President have suggested Mr Comey was dismissed because he was leading the investigation into alleged links between Mr Trump’s campaign team and Russia.
Mr Trump’s letter firing Mr Comey said he was losing his job on the recommendation of the Attorney General and that he was “not able to effectively lead the Bureau”.
Another former FBI director, Robert Mueller, is now in charge of the ongoing Russia-Trump investigation.
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His remit now also includes whether he President obstructed justice when he fired Mr Comey.