The actor said he had felt “ill” when the accusations had first surfaced and that no matter the outcome of the trial, he had would live with them for the rest of his life.
Depp is suing Heard for libel over a 2018 article she wrote in The Washington Post, which his lawyers say falsely implies he physically and sexually abused her.
The article does not mention him by name.
On Wednesday 20 April, Depp said he had read the article and “did not disagree” with parts of it, but that it was “clearly about me”.
“Reading the words that she had written about what was obviously referring to our relationship it was obviously relating to me, two years ago, it all matched up so it was clearly about me,” he said.
“She talks about the plight of women, not just in Hollywood but in general… and there were many things that I did not disagree with, in terms of this part of the article.”
He continued: “I understand anyone’s passion to right the wrongs that have been done over countless years against any being who has suffered at the hand of domestic violence, be it women, men, children.
“Some of this I can applaud… it was very well done with regard to violence against women or violence against anyone.”
It comes after the actor gave lengthy testimony in which he detailed a catalogue of events where Heard had allegedly been violent towards him, including one specific incident in which his finger was sliced off by a broken vodka bottle.
Depp told the court he was “probably the closest I’ve ever been” to having a nervous breakdown during the incident, which occurred in Australia in March 2015.
Recounting the incident in graphic detail, he described how his digit had been left looking “like Vesuvius” and that, in a state of shock, he had written on the walls in his own blood.
He also recalled other incidents where he claimed to have had to physically restrain Heard after she had “clobbered” him.
Asked about the 2018 article’s effect on him, he replied: “I felt ill, I felt sick in the sense that there was no truth in whatsoever and the fact that I was coming down on me so hard and so quickly and how it gained momentum round the world.
“You’re running between drops of lava, you’re running between raindrops that kill you, that destroy you.”
He continued: “I was very confused, I was very hurt because as I said before when you’re in a relationship and you do give your intimate truths to that person… then they start to use all that information and stretch it out into something that is completely shocking because it just didn’t happen.
“So I felt that it was incredibly cruel, and treachery. I don’t know if she wanted me to just be erased, or drop dead, or just let me stick around and allow her to ruin my life for a while and go out of her way to shame me and hurt my kids and hurt people who I have known for many many years.”
Depp added: “‘It was unfair’ is about the smallest understatement… it controlled my every waking second.”
Asked what he had lost, he said: “Nothing less than everything.
“When the allegations were made, when the allegations were rapidly circling the globe telling people that I was a drunken cocaine-fuelled menace who beat women… it’s over.
“No matter the outcome of this trial, the second the allegations were made against me… and turned into fodder for the media… I lost then.”
Beginning cross examination, Heard’s lawyer Benjamin Rottenborn reminded Depp that the lawsuit was not being brought over anything that the actress herself had done, prior to writing the article, and suggested that his career had already been in decline.
“I think it’s very easy to write a piece and put the finger on someone without saying their name,” Depp responded.
The trial at Fairfax County District Court, which is set to last a total of seven weeks, continues. Follow live updates here.