Asked if he thinks Russians "have something on Donald Trump," Comey said, "I think it's possible."
"It is stunning and I wish I wasn't saying it, but it's just ... it's the truth. I cannot say that [Trump is not subject to Russian blackmail]. It always struck me and still strikes me as unlikely, and I woulda been able to say with high confidence about any other president I dealt with, but I can't. It's possible."
The White House did not immediately respond to CNBC's request for comment about the Comey interview.
Comey also told ABC there is "certainly some evidence of obstruction of justice" when Trump asked him last year at the White House to if he could see his way to "letting Flynn go," referring to a criminal probe of fired National Security Advisor Michael Flynn.
"If he didn't know he was doing something improper, why did he kick out the attorney general and the vice president of the United States and the leaders of the intelligence community?" Comey asked, referring to Trump's actions before he asked about Flynn's case.
"I mean, why am I alone if he's — doesn't know the nature of the request?"
Comey's interview comes in advance of publication of his new book, "A Higher Loyalty: Truth, Lies, and Leadership" on Tuesday.
Comey's own firing last May by Trump set in motion the appointment of special counsel Robert Mueller by the Justice Department.
Mueller is investigating Russian interference in the 2016 presidential election, and possible collusion by Trump campaign officials in that meddling. Earlier this year, Mueller secured a guilty plea from Flynn for lying to the FBI, and got Flynn to cooperate with his ongoing probe of collusion and other matters.
Trump has repeatedly and angrily denied any such collusion. He also fumed about Mueller, and considered firing the special counsel, along with Attorney General Jeff Sessions, whose recusal from the Russia investigation let to Mueller's appointment by Deputy AG Rod Rosenstein.
Comey said he does not know "what's behind" Trump's reluctance to criticize Russian President Vladimir Putin in public.
"That mystified me even after President Trump became president, 'cause I discovered that he wouldn't criticize him even in private," Comey said.
"I can understand a president making a geopolitical decision that, 'I ought not to criticize an adversary country's leader for some reason publicly,' Comey said. "But I discovered President Trump wouldn't even do it privately, and I don't know why that is.'
After Comey said Trump was unfit to be president, he was asked if Trump should be impeached.
"I'll give you a strange answer," Comey said.
"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. People in this country need to stand up and go to the voting booth and vote their values," Comey said.
"We'll fight about guns. We'll fight about taxes. We'll fight about all those other things down the road. But you cannot have, as president of the United States, someone who does not reflect the values that I believe Republicans treasure and Democrats treasure and Independents treasure," he said. "That is the core of this country. That's our foundation. And so impeachment, in a way, would short-circuit that."
Comey's interview with ABC News and his new book have enraged Trump in recent days.
On Sunday morning, the president unloaded a series of nasty tweets about Comey.
In those tweets, Trump called Comey "slippery," a "slime ball" and predicted that he would be remembered "as the WORST FBI Director in history, by far!"