"When the allegations were made, were rapidly circling the globe, telling people I was a drunken, cocaine-fueled menace who beat women - suddenly in my 50s - it`s over," he said.
"I lost then," he added. "No matter the outcome of this trial, I will carry this for the rest of my days."
Attorneys for Heard, who just started their cross-examination of Depp late on Wednesday, have argued that she told the truth and that her opinion was protected free speech under the U.S. Constitution`s First Amendment. In opening arguments, Heard`s attorneys said Depp physically and sexually assaulted her while abusing drugs and alcohol.
A state court judge in Fairfax County, Virginia, is overseeing the trial, which is in its second week and is expected to last six weeks.
Less than two years ago, Depp lost a libel case against The Sun, a British tabloid that labeled him a "wife beater." A London High Court judge ruled he had repeatedly assaulted Heard.
Depp`s lawyers have said they filed the U.S. case in Fairfax County, outside the nation`s capital, because the Washington Post is printed at a facility there. The Washington Post is not a defendant in the case.
Depp and Heard, known for her roles in "Aquaman" and "Justice League," were married for roughly two years. Their divorce was finalized in 2017.
Heard has brought her own libel claim against Depp, saying he smeared her by calling her a liar. Heard's counterclaim, seeking $100 million, will be decided as part of the trial.