All the winner has to do is choose the winners of all 67 games in the 2014 "March Madness" tournament.
Buffett's Berkshire Hathaway will pay 40 yearly installments of $25 million to anyone who picks a perfect bracket in the contest.
A single winner could opt for a lump sum payment of $500 million, before taxes.
"We've seen a lot of contests offering $1 million for putting together a good bracket, which got us thinking, 'What is the perfect bracket worth?' We decided $1 billion seems right for such an impressive feat," Quicken Loans President and Chief Marketing Officer Jay Farner told the Chicago Tribune.
The contest is limited to the first 10 million legal U.S. residents to enter beginning March 3, with one entry per household. Quicken is offering prizes of $100,000 in home financing or remodeling to the 20 most accurate, but imperfect, bracket entries.
All registered participants will receive their tournament entry once the brackets are set March 16.
Sports Illustrated said the odds of picking a perfect NCAA tournament bracket are about 1-in-9.2 quintillion. That's nine followed by 18 zeros.
"I will invite him or her to be my guest at the final game and be there with a check in my pocket, but I will not be cheering for him or her to win," Buffett, 83, the fourth-richest individual on the planet told CNN. "I may even give them a little investment advice."