Bill Gates donate 4.6(bn)$ to the charity.
He remains the world's richest person, despite giving away 64 million shares in Microsoft.
The shares are equivalent to 5% of his total fortune, currently estimated to be $89.9bn.
Since 1994 Mr Gates, 61, and his wife Melinda have given away a total of $35bn in cash and stocks to a range of charitable causes.
The donation was made in June but became public on Monday following the filing of a document with the US Securities and Exchange Commission.
Mr Gates' share in Microsoft is now just 1.3%. Prior to this, Mr Gates gave away $16bn in Microsoft shares in 1999 and $5.1bn in 2000.
New money
The majority of all previous donations have been made to the Bill & Melinda Gates Foundation, which is primarily focused on reducing world poverty, combating infectious diseases and providing universal access to computers.
It is not known who the recipient of this latest donation is, however when federal documents are filed, it usually means new money is being given to a foundation, the Chronicle of Philanthropy reports.
In 2010, Mr and Mrs Gates and the well-known investor and philanthropist Warren Buffett created the Giving Pledge, and as of May 2017, 158 individuals or couples have agreed to contribute at least half of their wealth to charity.
This latest donation is the biggest charitable gift to have been made anywhere in the world so far this year.
The second largest was made by Mr Buffett, who donated almost $3.2bn to the Bill & Melinda Gates Foundation last month.
And the third biggest came from Dell Computer Corporation founder Michael Dell and his wife Susan.
In May the couple gave more than $1bn to their foundation, which focuses on children's issues and community initiatives.
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