Billionaire financier George Soros has written to the Financial Times, calling for Facebook bosses Mark Zuckerberg and Sheryl Sandberg to leave Facebook.
He argued the social media platform's refusal to remove political ads was "helping to get Donald Trump re-elected".
The letter comes as Mr Zuckerberg heads to Europe to call for light-touch government regulation.
His proposals have received a lukewarm response from European lawmakers.
Mr Zuckerberg wants regulation of harmful content on internet platforms to be different from existing rules governing the media and telecoms firms.
In response, European industry commissioner Thierry Breton said it was not "for us to adapt to this company, it's for this company to adapt to us".
'Obfuscating the facts'
In his short letter to the FT, Democratic party donor George Soros writes: "Mr Zuckerberg appears to be engaged in some kind of mutual assistance arrangement with Donald Trump that will help him to get re-elected.
"Facebook does not need to wait for government regulations to stop accepting any political advertising in 2020 until after the elections on 4 November.
"I repeat my proposal, Mark Zuckerberg and Sheryl Sandberg should be removed from control of Facebook."
He added that while he supports government regulation of social media platforms, he thinks Mr Zuckerberg is "obfuscating the facts" in his arguments for greater government control of the internet.
Mr Soros has been a vocal critic of Facebook and, in November 2018, the social network admitted it had hired a PR firm to run a smear campaign against him.
The firm Definers was hired to investigate the financier's links to the Freedom from Facebook campaign, which was seeking the firm's break-up.
Ms Sandberg initially denied knowledge of the hiring but later clarified that she had been told about the company but had forgotten its name.
Facebook v EC
Mark Zuckerberg is in Europe this week for meetings with various commissioners.
Ahead of these, he told delegates at the Munich Security conference that government regulation should fall "somewhere between" how existing media is regulated and rules governing telecom firms.
The social media platform also issued a document on content regulation this week, which lays out guidelines about how regulation around online content could work.
The four challenges it identifies are:
- how can content regulation reduce harmful speech while preserving free expression?
- how should regulation enhance the accountability of internet platforms?
- should regulation require internet firms to meet certain performance targets?
- should regulation define which harmful content should be prohibited on internet platforms?
Margrethe Vestager, the European Commission's executive vice president for digital affairs, also met Mark Zuckerberg.
She is due to unveil plans for how the EU will compete with the US and China on artificial intelligence technology later this week.