Sportsbooks at Gold Strike Casino in Tunica and Beau Rivage in Biloxi began accepting bets at noon local time.
Mississippi joins Delaware and New Jersey as states that have launched legal sports betting since the U.S. Supreme Court struck down the Professional and Amateur Sports Protection Act of 1992 in mid-May.
"Sports wagering is a rapidly growing, exciting new entertainment opportunity for our company," said Jim Murren, CEO of MGM Resorts, which owns Gold Strike and Beau Rivage. "We were proud to take the first sports wager in Atlantic City in June and today the first legal sports wager in two locations in Mississippi."
Mississippi is also the first state with legal sports betting in the college football hotbed of the Southeast. While New Jersey and Delaware prohibit wagers on games involving instate schools, the Magnolia State will offer betting on all professional and college teams, including Ole Miss and Mississippi State of the SEC.
Research firm Eilers & Krejcik Gaming projects that $750 million to $800 million will be wagered on sports annually when Mississippi's land-based sports betting market matures. Eventually, mobile sports betting apps will be offered, but only will be available on casino premises. In comparison, Nevada sportsbooks took nearly $4.8 billion in bets in 2017, according to state gaming control.
Caesars Entertainment announced this week that it expected to open sportsbooks at its Mississippi casinos before football season.
Ole Miss opens its season against Texas Tech on Sept. 1, in Houston. Mississippi State hosts Stephen F. Austin on Sept. 1
Former athletes, including longtime NFL running back Willis McGahee, politicians and even veteran oddsmaker Danny Sheridan were among the first to place legal wagers in Mississippi. The ceremonial bets came 26 years to the day after the first casino bet was made in Mississippi on Aug. 1, 1992.