The Duke and Duchess of Sussex will be questioned as part of a US defamation case brought by Meghan's half-sister.
Samantha Markle is suing Meghan for "defamation and injurious falsehoods" following the couple's interview with Oprah Winfrey in 2021.
She alleges she was defamed when Meghan "falsely and maliciously" said she was "an only child".
A motion brought by Meghan to stop depositions in the civil case from taking place was dismissed by a judge.
A deposition is a formal statement of evidence in the US, required to be taken of a witness or party to litigation by a court.
In the much-anticipated interview with Winfrey, the couple discussed their families, royal life and mental health.
The duchess' half-sister claimed, in a filing submitted in March, that Meghan made "demonstrably false and malicious statements" to a worldwide audience.
Documents obtained by PA News agency show the original motion.
They show Samantha Markle, who has MS and uses a wheelchair, brought the action, saying around 50m people in 17 countries had watched the Winfrey interview.
The motion says that it "disseminated false and malicious lies" and had subjected Samantha Markle to "humiliation, shame and hatred on a worldwide scale".
It adds that Meghan had used "the powerful resources of the Royal Family's public relations operation" to spread "lies worldwide" about Samantha Markle and their father Thomas Markle and describes it as a "premediated campaign to destroy their reputation and credibility".
It was done, the motion says, "to preserve and promote the false 'rags to royalty' narrative".
A motion brought by Meghan to stop depositions in the case from taking place was dismissed on Tuesday by Florida judge Charlene Edwards Honeywell.
The Times reports that she had argued that the jurors were being asked to decide what constitutes a "close" relationship between the half-sisters.
The defamation case comes after the publication of Prince Harry's memoir Spare in January and the couple's Netflix series last year.
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