The former UK deputy prime minister, 51, will take up the role from Monday and will spend a week at the company's Menlo Park headquarters.
He will then relocate to California in January with his wife Miriam and their three sons.
It comes as Mark Zuckerberg seeks to repair the company's reputation in the face of rows over transparency and the role of "fake news" on the platform following the 2016 EU referendum and the 2017 election of Donald Trump as US president.
Sir Nick's new title will be Vice President of Global Affairs and Communications at Facebook, reporting to chief operating officer Sheryl Sandberg.
He will succeed Elliot Schrage, who is set to stay on at the firm as an advisor.
It is understood Mark Zuckerberg wooed Sir Nick by saying he would have a leading role in shaping the company's strategy, the Financial Times reported.
Sir Nick is the most senior politician from Europe to work for Facebook and in a statement on his Facebook page he said he was looking forward to "an exciting new adventure".
He added that the firm and its apps, including Whatsapp and Instagram was "at the heart of some of the most complex and difficult questions we face as a society", over individual privacy, democratic integrity, the balance between free speech and prohibition online, artificial intelligence and the well-being of children.
He went on: "I believe that Facebook must continue to play a role in finding answers to those questions - not by acting alone in Silicon Valley, but by working with people, organisations, governments and regulators around the world to ensure that technology is a force for good.
"I am looking forward to being part of this endeavour."
The timing of the move to the United States may raise eyebrows after Mr Clegg took a prominent role in the campaign for a second "People's Vote" Brexit referendum.
Addressing this he added: "As someone who has spent a lifetime arguing for Britain's wholehearted commitment to Europe, it is of course a wrench to be leaving the public debate at a crucial time in the Brexit process.
"But the key decisions will soon pass to Parliament, of which I am no longer a Member, and once I had decided to take up this unique new challenge at Facebook, I felt it was best to get going sooner rather than later."
The politician, who lost his Sheffield Hallam seat at last year's general election, was leader of the Lib Dems from 2007 to 2015.
Facebook has come under intense scrutiny following the Cambridge Analytica scandal and alleged election meddling.
The firm already has links to the Lib Dems as Richard Allan, its public policy chief for Europe, the Middle East and Africa, is a peer for the party.
Sir Nick succeeded Mr Allan as MP for Sheffield Hallam.