Binion's Horseshoe is internationally known as the home of the World Series of Poker. It was "Nick the Greek" Dondolos who first approached Benny Binion in 1949 with the idea for a high-stakes poker marathon between top players. Binion agreed, with the stipulation that the game be open to public viewing. The competition, between Dondolos and the legendary Johnny Moss, lasted 5 months with breaks only for sleep. Moss ultimately won about $2 million. As Dondolos lost his last pot, he rose from his chair, bowed politely, and said, "Mr. Moss, I have to let you go."

In 1970, Binion decided to re-create the battle of poker giants, which evolved into the annual World Series of Poker. Johnny Moss won the first year, and went on to snag the championship again in 1971 and 1974. Thomas "Amarillo Slim" Preston won the event in 1972 and popularized it on the talk-show circuit. In 2002, there were more than 7,595 entrants from over 22 countries, each ponying up the $10,000 entrance fee, and total winnings were in excess of $19 million (the tournament was also televised on ESPN). During one memorable year, the participants included actors Matt Damon and Edward Norton, fresh from Rounders, a movie in which they played a couple of card sharks. They decided to try out their newly acquired moves against the pros, who were unhappy that these kids were barging in on their action, and so, rumor has it, offered a separate, large bounty to whatever player took them out. Both actors got knocked out on the first day but took it with good grace and apparently had a blast.