Attorneys-general from California, Colorado, Kentucky and New Jersey are seeking extensive financial damages plus changes to how the company operates Facebook and Instagram.
Twenty-nine states sued the tech giant in 2023 over child safety and privacy - the other 25 will go to trial later.
The company also faces lawsuits in state courts.
The lawsuit accuses the social media giant of contributing to the youth mental health crisis by knowingly and deliberately designing features that get children addicted to its platforms.
It also argues that Meta routinely collects data on children under 13 without their parents' consent, in violation of federal law.
"This week, we're in court with the largest consumer protection lawsuit in American history. We'll show a jury that Meta concealed what it knew about the harm its products cause young people because looking away was more profitable," said Kentucky Attorney-General Russell Coleman in a statement.
Meta said it believes it has a strong case.
"We are proud of our record in protecting teens on our platforms and the amount of effort that we've put into developing protections over the years, even before these cases were ever filed, and continuing to the present day. We look forward to showing the judge and the jury those facts in court," the company said in a statement.
US District Judge Yvonne Gonzalez Rogers in Oakland will oversee the proceedings starting on Tuesday, which are expected to last six to eight weeks, with Meta CEO Mark Zuckerberg and other executives and former employees testifying.
Gonzalez Rogers, appointed to the bench by president Barack Obama in 2011, has overseen a bevy of complex, high-profile cases involving Big Tech.
These include Elon Musk's lawsuit against OpenAI and its founders as well as Epic Games' lawsuit against Apple over its app store.
The trial is the latest in an avalanche of lawsuits against Meta Platforms and other social media companies including Google's YouTube, TikTok and Snap, over arguments that their platforms harm young people, illegally collect their data and are deliberately designed to addict them.
10°C