The ticket was sold at the Speedway fuel and convenience store on East Touhy Avenue in Des Plaines, Illinois, a Chicago suburb.
Going into the draw on Friday night, the jackpot was estimated at $1.28 billion, but swelled as people piled in to try their luck.
The still-to-be-identified holder of the winning ticket, which would have cost $2 to buy, matched all six numbers.
They have the choice of a lump-sum payment of $780.5 million or an annual payout over 30 years.
Most winners go for the lump sum, which comes with a hefty tax bill, according to the Mega Millions website.
The winning numbers for the jackpot, which had been rolling since it was last won at $20 million in Tennessee on April 15, were 13, 36, 45, 57 and 67, plus the mega ball 14.
Officials said this is the largest jackpot ever won in the state of Illinois and the second largest in the 20-year history of the game, topped only by the $1.537 billion won in South Carolina in October 2018.
The latest Mega Millions lottery was held in 45 states, Washington, D.C., and the U.S. Virgin Islands.
Half of the proceeds from the sale of each Mega Millions ticket remains in the state where the ticket was sold; the money supports lottery beneficiaries, such as education or public employee pensions, and retailer commissions.
Retailers get a 1.0% selling bonus for the winning ticket, capped at $500,000, according to Harold Mays, director of the Illinois Department of the Lottery.