"Biloxi was the first place I ever made a dollar professionally," Buffett said Sunday in New Orleans.
The 65-year-old Mississippi native has 26 albums, three No. 1 New York Times best-selling books and developed the Margaritaville Cafe and Cheeseburger in Paradise restaurant chain.
"Actually growing up down there, it's a big part of my family history and musical history," Buffett said.
"And then you throw in a couple of hurricanes and an oil spill ... I care enough about this place to have wanted to do something to help recover from those things, and that's how [the casino] came about."
Buffett said the waterfront complex, which opens Tuesday, will feature special indigenous touches, including memorabilia.
The singer hits the road with his Coral Reefer Band May 30. He plans to record a new album this fall.