Facebook founder and his wife gained the accolade after a donation of 18 million Facebook shares to a Silicon Valley foundation.
The donation, worth more than $970 million, was the largest in the US in 2013.
The gift outstripped philanthropists such as Bill and Melinda Gates, the Chronicle of Philanthropy said.
Mark Zuckerberg and his wife made the $970 million donation to the Silicon Valley Community Foundation, a charity that manages and distributes charitable funds.
The shares have helped to make the foundation one of the largest in the US, the Chronicle of Philanthropy said.
Over the past two years, Mark Zuckerberg and Priscilla Chan have donated about 36 million Facebook shares to the foundation.
Funds have broadly been distributed to education and health, with $5 million being distributed to a health clinic in East Palo Alto, for example.
Philanthropists who have previously headed the list, such as Microsoft co-founder Bill Gates and his wife, Melinda, have been making good on previous years’ pledges.
Bill and Melinda Gates gave their foundation slightly more than $181.3 million last year, and continue to honor a pledge of about $3.3 billion they made in 2004.
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