The Internet entrepreneur told a packed auditorium in San Francisco that "it takes courage to choose hope over fear" and encouraged Americans to unite rather than divide and segregate.
He also criticised “fearful voices talking about building walls”, which comes after Trump pledged to build a wall across the border between the US and Mexico.
Zuckerberg said: "As I look around the world, I’m starting to see people and nations turning inward, against the idea of a connected world and a global community.
The path forward is to bring people together, not push them apart Mark Zuckerberg
"I hear fearful voices calling for building walls and distancing people they label as ‘others’.
"I hear them calling for blocking free expression, for slowing immigration, for reducing trade, and in some cases even for cutting access to the internet.
The married 31-year-old also stressed in his address that immigration was essential to the economic success of the country.
He continued: "It takes courage to choose hope over fear. People will always call you naive but it’s this hope and optimism that’s behind every important step forward.
"If the world starts turning inward, our community will just have to work harder to bring people together.
"I hope that we have the courage to see that the path forward is to bring people together, not push them apart."
Trump has faced criticism from British comedian and US talk-show host John Oliver, 'The Last Leg' presenter Adam Hills, and several Members of Parliament.
The Republican frontrunner recently lost the Wisconsin Primary but has so far notched up the most number of 'delegates' from state election races, attaining 743, topping second-place's Ted Cruz, who has 545.