The couple gained the accolade after a donation of 18 million Facebook shares to a Silicon Valley foundation.
The donation, worth more than $970m (Â£590m), was the largest in the US in 2013.
The gift outstripped philanthropists such as Bill and Melinda Gates, the Chronicle of Philanthropy said.
Mr Zuckerberg and his wife made the $970m 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, Mr Zuckerberg and Ms Chan have donated about 36 million Facebook shares to the foundation.
Funds have broadly been distributed to education and health, with $5m 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.
Mr and Mrs Gates gave their foundation slightly more than $181.3m last year, and continue to honour a pledge of about $3.3bn they made in 2004.
Facebook founder Mark Zuckerberg and his wife Priscilla Chan have been named joint top US philanthropists for 2013.