Buono was born and raised in The Bronx, New York City, New York, in a blue-collar family with two brothers and a sister. She is of Italian descent.

Buono attended Fiorello H. LaGuardia High School and is a 1995 graduate of Columbia University with a double major in English and political science. She earned her degree in three years. She made her acting debut in Harvey Fierstein\'s play Spook House.

Buono continued stage work both on Broadway and Off Broadway, and started her film career opposite Ethan Hawke and Jeremy Irons in Waterland (1992). Much of her work has been in indie films such as Chutney Popcorn (1999), Happy Accidents (2000), Next Stop Wonderland (1998) and Two Ninas (1999), which she co-produced. In 1999, she played a small role as a young Gerry Cummins in the TV movie, Deep in My Heart (1999).

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