The TV star, who plays corrupt politician Enoch 'Nucky' Thompson in the crime drama, beat Michael C. Hall (Dexter), Bryan Cranston (Breaking Bad), Jon Hamm (Mad Men) and Hugh Laurie (House) to win the SAG's first trophy.
Taking the stage to accept his win, Buscemi paid tribute to his fellow nominees, and Boardwalk's cast and crew, saying: "Im very nervous. I want to tip my hat to Bryan Cranston, Michael C. Hall, Jon Hamm and Hugh Laurie, it's an honour to be nominated with you. I want to thank the amazing crew on Boardwalk, they've been a second family to us."
The series is also nominated for outstanding ensemble at the ceremony, which is taking place at the Shrine Exposition Center in Los Angeles.