Born and raised in Meadville, Pennsylvania, she graduated from high school in 1975. Soon after, she enrolled in college while also entering a beauty pageant, which led to a contract with the Ford modeling agency, after which she set off to conquer Paris and Milan.

After ending her modeling career, Stone moved to New York and soon made her debut in a minor role in Woody Allen's film Stardust Memories, after which she mostly appeared in episodes of various TV series. She also played supporting roles in the films Irreconcilable Differences and King Solomon's Mines. Later she played the girlfriends of Steven Seagal (Above the Law), Arnold Schwarzenegger (Total Recall), and Sylvester Stallone (The Specialist).

Stone achieved her greatest fame for her role in the film Basic Instinct. She also played a serial killer's victim in Sliver, and then the role of the frigid wife of Richard Gere's character in the film Intersection. For the role of the main character's wife (played by Robert De Niro) in Martin Scorsese's film Casino, Stone won a Golden Globe and received the only Oscar nomination of her career for Best Actress (the win went to Susan Sarandon for her role in Dead Man Walking).

A whole series of Stone's roles were nominated for the Golden Raspberry anti-award, including being named Worst Actress in 1995 (for the films Intersection and The Specialist), and also in 2007 for the film Basic Instinct 2.