The former Hollywood power couple are both expected to give evidence in person at the trial, and high-profile figures including James Franco, Paul Bettany and Elon Musk are scheduled to give testimony.
Depp is suing his former partner for libel over a 2018 op-ed she wrote in the Washington Post, in which she discussed her experiences of domestic abuse.
The actor’s lawyers say the article falsely implies Heard, 35, was physically and sexually abused by Depp when they were married.
Depp, 58, has said the accusations have made it difficult for him to get the sorts of roles he once did.
The piece was titled: "I spoke up against sexual violence — and faced our culture’s wrath. That has to change."
Amber Heard Victoria Jones
The article does not mention Depp by name.
Heard’s lawyers are expected to argue she should be immune from the libel suit because of a Virginia law known as an anti-Slapp provision (Strategic Lawsuit Against Public Participation).
The provision is designed to protect people from nuisance lawsuits when they speak about matters of public concern.
Heard’s lawyer, Elaine Bredehoft, has argued the article addresses a very serious issue of public concern: preventing domestic violence.
The actress has also filed a counterclaim for defamation against Depp because of statements his lawyer made about her.
The case is being brought in Virginia, rather than in California where the actors live, because the Washington Post’s online editions are published through servers located in Fairfax County.
Depp’s lawyers say one of the reasons they brought the case in Virginia is because the state’s anti-Slapp law is not as broad as the one in California.
The lawsuit, taking place at the Fairfax County District Courthouse, seeks 50 million dollars (£38.2million) in damages.