Zuckerberg said the world's largest social network would start "aggressively opening up remote hiring", expecting that about half its workforce would work remotely over the next five to 10 years.
He emphasised that the 50 per cent figure was his estimate and not an official announcement.
Zuckerberg pitched the idea as both a matter of satisfying employee desires and also as an effort to create "more broad-based economic prosperity".
However, 40 per cent said this would not be practical due to the nature of their jobs. The remarks came less than two weeks after rival Twitter said it would let some employee work from home "forever".
If you want to work for Facebook from your house in Peoria, Ill., don't expect a Palo Alto, Calif. -sized paycheck.
Facebook had expanded its Menlo Park headquarters with a huge hangar-style campus built by star architect Frank Gehry.
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At Facebook, more than 95% of full-time employees have been working from home during the COVID-19 pandemic.
Zuckerberg said that in a company survey, of the people who said they would want to work remotely full time, about 45% were "pretty confident" that they would move to another place if they had that opportunity, with an additional 30% saying they "might" move. But according to Zuckerberg, productivity remains up for more than half of the company's workers.
But for employees, there is a potential downside to the remote work.
The company also sees benefits in hiring. "Certainly being able to recruit more broadly, especially across the USA and Canada to start, is going to open up a lot of new talent that previously wouldn't have considered moving to a big city".
"We'll adjust salary to your location at that point", said Zuckerberg, who said the adjustment would be necessary for taxes and accounting.
The decision comes just hours after Spotify told its employees they can work remotely through the end of the year. "If you're experienced, if you're at a certain level within the company, if you have good performance ratings, if you're on a team that's going to support remote work, and if you get approval, then you'll be able to know now that you'll be a permanent remote worker".
"I think the best people, you're going to have to pay them regardless of where they live or you're going to lose them to a competitor", he said.