Brennan accused the executive branch of twisting the justice system for political ends.
“And clearly there is a corruption and a perversion of the justice system right now within the executive branch,” he added.
On Thursday, a grand jury indicted Comey on charges of making a false statement and obstructing a congressional proceeding.
Comey has denied any wrongdoing.
Democrats swiftly denounced the indictment.
“The malicious prosecution against James Comey has no apparent basis in law or fact, and lawyers of good conscience in the department know it,” said House Minority Leader Hakeem Jeffries, D-N.Y.
Brennan, a longtime Trump critic, defended Comey’s integrity.
“I’ve never doubted” the former FBI director’s character, he said, suggesting the case reflected political retribution rather than genuine law enforcement concerns.
Trump welcomed the indictment and signaled more could follow. He said he hoped for further charges against “corrupt, radical-left Democrats.”
Potential targets include New York Attorney General Letitia James; Sen. Adam Schiff, D-Calif.; former Director of National Intelligence James Clapper; and Brennan.
“I don’t know what may be coming my way, but I’m not going to do things that are inconsistent with my ethics and my values and what it is that I believe is important,” Brennan said.
“And I think more people have to speak out when they see injustice, when they see a government that is abusing its authority and its power.”
Brennan said no legitimate case exists against him, pointing to prior Justice Department reviews.
“You know, I don’t see any case against me. I have looked back on all of my actions and decisions,” he said.
He added that investigations conducted by former special counsel John Durham confirmed that his conduct fell within the scope of legal authority.
The former CIA chief urged Republicans to oppose what he called politically driven prosecutions.
“I think more and more people have to speak out. And I’m waiting for those Republicans in Congress to come to their senses, because the damage that’s being done to this country and the dangerous times that we’re in, I think too many Americans do not appreciate the extent of that,” Brennan said.