Zuckerberg said in a keynote speech yesterday at an Asia-Pacific leaders' summit that while globalisation and interconnectedness have their problems, the world must fight the urge to "disconnect".
"As we are learning this year in election after election, even if globalisation might (boost) prosperity, it also creates inequality. It helps some people and it hurts others," he said.
The 32-year-old billionaire said there was a "fundamental choice" to make in reacting to that inequality.
The second option is better, but also harder, he said in his speech at the Asia-Pacific Economic Cooperation (APEC) summit in Lima, Peru.
"Disconnecting is relatively easy. But connecting requires making big investments in infrastructure and generating the political will to make hard, long-term decisions," he said.
Facebook has made headlines with its projects on connectivity and internet access.
The company has helped more than 40 million people get online, Zuckerberg said.
His comments came amid deep global uncertainty in the wake of the unexpected poll results in the US and Britain.
Trump and the Brexit camp both appealed to working-class voters who feel threatened by globalisation and immigration, running on a populist politics of disillusionment with an increasingly borderless world.
Trump vows to protect American jobs from cheaper labour overseas, while Brexit campaigners promise British workers will fare better outside the European Union than in it.
Zuckerberg has dismissed claims his company influenced the vote as "pretty crazy".
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