The Ocean's Thirteen star became the first winner of Sunday's (12Jun11) ceremony in New York, claiming victory over Edie Falco (The House of Blue Leaves), Judith Light (Lombardi), Joanna Lumley (La Bete) and Elizabeth Rodriguez (The Motherf**ker with the Hat) for her role as a frustrated doctor in the fight against AIDS in a revival of the Larry Kramer play.
Taking to the stage at The Beacon Theatre, Barkin hailed her win as the "proudest moment in my career" and paid tribute to her theatre colleagues.
She told the crowd, "Thank you for the way you've embraced me and welcomed me into your community. I am so grateful and so humbled to be in your company."
South Park creators Trey Parker and Matt Stone were also early winners at the 65th Annual Tony Awards, which celebrates the best of Broadway, earning the prize for Best Original Score for their work on The Book of Mormon. The musical is nominated for a total of 14 Tonys.
Host Neil Patrick Harris opened the awards show with a comical song and dance routine titled It's Not Just For Gays Anymore, and stepped into the audience to share the microphone with the likes of TV funnyman Stephen Colbert and model/actress Brooke Shields, although the beauty flubbed her lines three times and had to refer to a cue card to remember her lyrics.
Daniel Radcliffe and Tony nominee John Larroquette performed Brotherhood of Man from their musical How to Succeed in Business Without Really Trying, while John Leguizamo also took to the stage to share a sketch from his one-man show Ghetto Klown.
Guests in the star-studded audience included Al Pacino, Whoopi Goldberg, Hugh Jackman, James Earl Jones and Vanessa Redgrave.