The young billionaire, who is married to Chinese-American Priscilla Chan, had set himself the goal of learning Mandarin in 2010.
After his speech, he shared his accomplishment with his followers on Facebook along with a a video of the speech with English subtitles.
"I just gave my first ever speech in Chinese at Tsinghua University in Beijing -- on why you need a strong sense of mission to change the world.
Zuckerberg had joined the board of Tsinghua's School of Economics and Management last year.
"This is a great centre of innovation and many of the students here will become global leaders in technology, business and government," he said.
In September, Zuckerberg had conversed with Chinese President Xi Jinping in Mandarin at a meeting with technology chiefs.
These could be seen as part of efforts being made by the social networking giant to woo the world's largest Internet population. Interestingly, Facebook is banned in mainland China and remains untapped for Facebook that has over 1.3 billion users globally.
He is scheduled to address a Townhall at the Indian Institute of Technology, Delhi. India is home to over 130 million users, making it the second largest user base for the world's largest social networking site after the US.
Zuckerberg also shared a post about his run around Xi'an -- one of the ancient capitals in China's history and the starting point of the Silk Road.
"I love taking my team for a run whenever we travel to a new city. It's a great way to see a city before a busy day of events, and it's also a great way to wake up, get energy and kick jet lag. We ran the length of the ancient city wall in the rain for 8.6 miles," he wrote.
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