As Zuckerberg took the stage, he briefly mentioned what the audience of about 8,000 developers, analyst and press expected -- virtual reality and artificial intelligence.
Then his speech quickly took a different turn and, without mentioning Trump by name, Zuckerberg took on the controversial businessman and his campaign platform.
"I want to talk about our mission for a moment and why I care about it so much," he said. "It's more important now than it's ever been. We stand for connecting every person for a global community, for bringing people together and giving people a voice... The Internet has enabled all of us to access and share more information than ever before."
However, Zuckerberg said he's been troubled by a new trend that he's seeing.
"Now, as I look around and travel around the world, I'm starting to see people and nations turning inward against this idea of a connected world," he said. "I hear fearful voices call for building walls and reducing trade and stopping immigration."
On the campaign trail, Trump has garnered a lot of headlines for calling for temporarily stopping immigration of Muslims, and for calling on Mexico to pay to build a wall on its border with the United States.
Ezra Gottheil, an analyst with Technology Business Research, said he's not too surprised that Zuckerberg would so sharply interject a political point into the keynote of his company's largest conference.
"Zuckerberg has been pretty open about his opinions," said Gottheil. "He's pretty outspoken and, in fact, a lot of his technical and product messages could be viewed as political. He's positioned his entire company as connecting people instead of isolating them."
To wrap up his point today, Zuckerberg encouraged people to not make their choices based on fear.
"It takes courage to choose hope over fear. You have to be optimistic to think that you can change the world," Zuckerberg said. "Instead of building walls, we can build bridges. And instead of dividing people, we can pull people together. We do it one innovation at a time, day after day after day. That's why I think the work we're all doing together is more important now than it's ever been before."