Comey's remarks are the latest salvo in a war of words with Trump, who excoriated the former FBI director on Twitter, again calling him a "slimeball" and suggesting he should be jailed.
The wide-ranging interview with ABC News also came ahead of the release of Comey's memoir, A Higher Loyalty: Truth, Lies and Leadership, in which he details his interactions with the Republican president.
"I think he's morally unfit to be president," Comey said, in his first televised interview since being fired in May last year.
The former federal prosecutor pointed to how Trump "talks about and treats women like they're pieces of meat" and "lies constantly about matters big and small and insists the American people believe it."
"Values matter," Comey said. "This president does not reflect the values of this country."
Comey also said that serving in Trump's administration poses a serious ethical dilemma.
"The challenge of this president is that he will stain everyone around him," he said .