In an interview with the BBC, the Facebook founder said that fake news, polarised views and "filter bubbles" were damaging "common understanding".
He said people had been left behind by global growth, sparking demands to "withdraw" from the "connected world".
In a call to action, he said people must not "sit around and be upset", but act to build "social infrastructures".
"When I started Facebook, the mission of connecting the world was not controversial," he told me.
"It was as if it was a default assumption that people had; every year the world got more connected and that seems like the direction things were heading in.
"Now that vision is becoming more controversial."
He told the BBC: "There are people around the world that feel left behind by globalisation and the rapid changes that have happened, and there are movements as a result to withdraw from some of that global connection."
Mr Zuckerberg's interview comes alongside the publication of a 5,500-word letter he has written about the future of Facebook and the global economy.
In it Mr Zuckerberg quotes Abraham Lincoln who spoke of acting "in concert", and talks about "spiritual needs", civic engagement and says that many people have "lost hope for the future".
"For a couple of decades, may be longer, people have really sold this idea that as the world comes together everything is going to get better," he said.
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"I think the reality is that over the long term that will be true, and there are pieces of infrastructure that we can build to make sure that a global community works for everyone.
"But I do think there are some ways in which this idea of globalisation didn't take into account some of the challenges it was going to create for people, and now I think some of what you see is a reaction to that.
"If people are asking the question, is the direction for humanity to come together more or not? I think that answer is clearly yes.
"But we have to make sure the global community works for everyone. It is not just automatically going to happen.
"All these different kinds of institutions, whether they are governments, or non-profits, or companies, need to do their part in building this infrastructure to empower people so that it creates opportunities for everyone, not just some people.
"If you are upset about the direction things are going in, I hope you don't just sit around and be upset, but you feel urgent about building the long term infrastructure that needs to get built," Mr Zuckerberg said.
I asked him whether he felt President Trump agreed with his view that "bringing people together" and "connecting the world" would lead to greater progress.
Mr Zuckerberg did not, famously, attend the round-table of technology leaders hosted by the new president.
"I don't think I am going to speak to that directly," he answered carefully. "You can talk to him, you can look at what he has said to get a sense of that.
"The thing that I will say is that a lot of folks will look at this through the lens of one or two events, and I really do think this is a broader trend.
"I have been talking about this for a long time, since before recent elections both across Europe and Asia and the US.
"A lot of today's biggest opportunities will come from bringing people together - whether that is spreading prosperity or freedom, or accelerating science, or promoting peace and understanding."
Mr Zuckerberg said: "A lot of challenges we face today are also entirely global - fighting climate change or ending terrorism, or ending pandemics, or when a civil war in one country leads to a refugee crisis across different continents.
"These are inherently global things and require a different level of infrastructure than we've had historically."
Would you like to meet President Trump? I asked.
"I would like that not be the focus of this. I don't really have much comment on that. It somewhat detracts from the focus of what we are trying to do here."
There has been speculation that Mr Zuckerberg could be contemplating a political career, and even suggestions that he will run for US president in 2020 - rumours he has flatly denied.
I said the political tone of the manifesto would do little to dampen speculation about where he sees himself longer term.
Could he imagine himself going into politics? "I am not doing that now, it's not the plan," he said. "The thing I really care about is connecting the world."
Facebook has been attacked for not doing enough to tackle "fake news" - untrue stories which claimed, for example, that the Pope backed Mr Trump - which have appeared prominently on its news feeds.
In Germany, there has been controversy after a Green MP was quoted in a Facebook post defending an asylum seeker from Afghanistan who had raped and murdered a German student.
The MP, Renate Kuenast, had never said what was attributed to her by a right-wing extremist organisation.
Ms Kuenast said she found it hard to accept that "Zuckerberg earns billions, shows off with all his charitable donations, and at the same time allows Facebook to become a tool of extremists".
Mr Zuckerberg said he understood the importance of tackling fake news.
"Accuracy of information is very important," he said in the 5,500-word letter, published on Thursday. "We know there is misinformation and even outright hoax content on Facebook.
"We've made progress fighting hoaxes the way we fight spam, but we have more work to do.
"We are proceeding carefully because there is not always a clear line between hoaxes, satire and opinion."
But Mr Zuckerberg added: "In a free society, it's important that people have the power to share their opinion, even if others think they're wrong.
"Our approach will focus less on banning misinformation, and more on surfacing additional perspectives and information, including that fact checkers dispute an item's accuracy."
He told me that "polarisation and sensationalism" also undermined "common understanding".
And he admitted that social media - which deals in short, often aggressive, messages - had been part of the problem.
"In some places [it] could over simplify important and complex topics and may push us to have over simplified opinions of them," Mr Zuckerberg said.
"And I think it is our responsibility to amplify the good effects and mitigate the negative ones so we can create a community that has a common understanding
"There is a lot of research that shows we have the best discourse when we connect as whole people rather than just opinions.
"If I get to know you on the values that we have in common or even the interests that we share it is a lot easier to have a debate about something that we disagree about productively than if we just meet and go head to head on something without understanding our common humanity."
Some may argue there is a question of legitimacy here, that no one voted for Mark Zuckerberg and question his right to outline - and attempt to execute - a vision of the world.
And what about those controversies over taxes paid, or privacy, or vast profits in an age when inequality is as much a factor behind the present dim view of many in the political and business establishment as any perceived failures of globalisation.
"There are a lot of areas that I know we need to improve and I appreciate the criticism and feedback and hope we can continue to do better on them," Mr Zuckerberg said, pointing out that he is donating 99% of his Facebook shares - worth Â£36bn ($45bn) - to the charitable foundation he runs with his wife, Priscilla Chan.
"Being a good corporate citizen is really important," he said. "We operate in a lot of different countries all around the world.
"We need to be help build those communities and that is what I am trying to do in my personal philanthropy - setting an example hopefully for other entrepreneurs who will build things in the future for how you should give back to the community and to the world.
"I care deeply about all of this, and it is a work in progress."
Mark Zuckerberg has revealed deep-seated concerns that the tide is turning against globalisation.