The former UK deputy prime minister said it was the "right time for me to move on" from his role as president of global affairs at Facebook's parent company.
Clegg will be replaced by his current deputy and Republican Joel Kaplan - who will be responsible for handling the social media giant's relationship with returning US president Donald Trump.
The former Liberal Democrat leader added that he would spend "a few months handing over the reins" and representing Facebook at international meetings before moving on to "new adventures".
He said: "As a new year begins, I have come to the view that this is the right time for me to move on from my role as president of global affairs at Meta.
"It truly has been an adventure of a lifetime!"
The ex-politician continued: "My time at the company coincided with a significant resetting of the relationship between 'big tech' and the societal pressures manifested in new laws, institutions and norms affecting the sector.
"I hope I have played some role in seeking to bridge the very different worlds of tech and politics - worlds that will continue to interact in unpredictable ways across the globe."
Clegg's departure comes just weeks before Trump begins his second term in the White House and his replacement will have to mend a strained relationship between the president-elect and Meta.
Trump has repeatedly accused Meta and other platforms of censorship and silencing conservative speech.
He also threatened Facebook CEO Mark Zuckerberg with imprisonment if he interfered in the 2024 presidential election and even branded the social media company as an "enemy of the people".