The jackpot swelled after 16 consecutive draws had failed to produce a winning ticket.
No-one has yet come forward to claim the prize.
Tickets had been selling at a rate of 130,000 a minute nationwide, but the odds of scooping the top prize had been calculated at one in 175 million.
Lottery officials said the winning tickets were sold in Arizona and Missouri, but it was not yet clear whether they had been bought by individuals or groups.
Statisticians calculated that a player had more chance of becoming US president, dying from a bee sting or getting struck by lightning than hitting the jackpot.
The numbers drawn late on Wednesday were 5, 23, 16, 22, 29 and 6.
The prize fund had apparently been boosted by late purchases by those who rarely play the lottery.
“I’ve been thinking about winning this money and what I’d do with it,” first-time ticket buyer Pat Powell told the Associated Press in Atlanta, Georgia.
“Let me just join the hype and just do it.”
In New York, another player, Nelson Batista, told Reuters news agency that if he won: “Maybe I’d change my face and my whole body and I make myself more younger.”
Forty-two US states, the District of Columbia and the US Virgin Islands participate in the Powerball lottery.
Officials doubled the price of Powerball lottery tickets in January to $2.
Despite an initial drop in sales, revenue is reportedly about 35% higher than 2011 figures.
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