Comey's remarks are the latest salvo in a war of words with Trump, who excoriated the former FBI director on Twitter earlier in the day, again calling him a "slimeball" and suggesting he should be jailed.
The wide-ranging interview with ABC News also came ahead of Tuesday's 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 told ABC, which aired an edited version of the interview but published a full transcript.
"And the question is, how much stain is too much stain and how much stain eventually makes you unable to accomplish your goal of protecting the country and serving the country?"
But while Comey sharply criticized Trump, he said he hopes the president is not impeached.
"I hope not because I think impeaching and removing Donald Trump from office would let the American people off the hook and have something happen indirectly that I believe they're duty bound to do directly."