The Boyd Gaming-owned casino has teamed up with FanDuel Sportsbook.
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The first bet was by former Eagle's tight end Brent Celek. His $20 wager was that Bryce Harper would hit 34 home runs this year.
He said he figures its a safe bet.
Inside the sports betting facility, that is off the lobby of the main casino, there are 29 video displays, seven teller windows and seating for 30 customers.
Bets are taken on a wide range of professional and college sports, baseball, basketball, golf, boxing, auto racing, even cricket.
Tom Evanik of Collegeville said he was a first time sports better. He bet $25 the University of Maryland basketball team will win its conference tournament.
Asked if he felt good about the wager he said, "It's my wife's team, I will see. It's my birthday, I could be lucky."
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The goal to open the sportsbook before NCAA March Madness begins next week.
"The first weekend is always the busiest weekend for March Madness because all the games that are going on Thursday and Friday and then Saturday and Sunday," Valley Forge Casino manager David Zerfing explained.
This will be the first national college basketball tournament since a U.S. Supreme Court decision that cleared the way for all states to legalize sports gambling.
It's expected some fans who want to gamble on the early bracket games will book at least some of the Valley Forge Casino's 440 hotel rooms so they don't have to travel far to place their bets.