By one measure, the purchase is the feather in the cap for Buffett's investment portfolio. It is the largest purchase Berkshire Hathaway has ever made, the firm said.
"Our country's future prosperity depends on having an efficient and well-maintained rail system," Buffett, known as the Sage of Omaha, said in a statement.
"Most important of all, however, it's an all-in wager on the economic future of the United States. I love these bets," Buffett said.
Mathew Rose, the railroad's president and chief executive officer said the investment "will allow BNSF to focus on future needs of our railroad, our customers and the U.S. transportation infrastructure."
The deal values BNSF at $100 per share, to be paid in stock and cash. Berkshire Hathaway is also assuming about $10 billion in outstanding debt with the purchase.
On Wall Street, stocks stumbled early Tuesday, but railroad shares spiked, jumping 11.58 percent in the early going.
The deal, expected to close in the first quarter next year, is subject to regulatory review and requires approval of two-thirds of the corporation's outstanding shares.