The deal includes Fox’s 39% stake in satellite broadcaster Sky, and the 20th Century Fox film studio,
Fox’s remaining assets, including Fox News and Sports, will form a new company.
The deal ends more than half a century of media expansion by Fox owner Rupert Murdoch, who is 86 years old.
He turned a single Australian newspaper he inherited from his father at the age of 21 into one of the world’s largest news and film empires.
Mr Murdoch’s shift to selling assets rather than buying them has come as a surprise to those who expected him to hand over the businesses to his sons, James and Lachlan.
Disney will buy the Fox assets for $52.4bn in stock, plus about $13.7bn net debt, leaving the value of the deal at about $66.1bn.
It is not clear how the deal will be received by US antitrust regulators.
The US Department of Justice recently sued to block AT&T’s $85.4bn deal to buy Time Warner, on the basis that it will raise prices for consumers and competitors.
Fox’s proposed deal to buy the remainder of Sky is being already investigated by the UK Competition and Markets Authority (CMA), which is due to publish provisional findings in January.
Disney chief executive Bob Iger will remain in his role until the end of 2021.
Fox is selling assets including its FX and National Geographic cable channels and media company Star India.
Disney also will buy Fox’s stake in the Hulu video streaming service, giving it majority control of a competitor to Netflix.