As part of the all-stock purchase, Disney will acquire the 20th Century Fox film and television conglomerate and assume nearly $14 billion in Fox debt.
The total value of 21st Century Fox's assets is estimated at $66.1 billion, Disney said.
Twenty-first Century Fox was established in 2013 in a spinoff venture by Australian businessman Rupert Murdoch's News Corporation.
Disney announced the major deal in a transaction call Thursday morning.