Hepburn died surrounded by friends and family, ABC News reported.
She was the only actor or actress to have been nominated for 12 Academy Awards, and the only woman to win four as best actress -- three of them after age 60, ABC said.
She was named the greatest American female screen actress of all time by The American Film Institute.
Her frequent co-star, Cary Grant, called Hepburn "the most completely honest woman I've ever met."
She was born May 12, 1907, in Hartford, Conn. Her father was a surgeon and her mother was a famous suffragette and birth control activist.
Hepburn was deeply affected by the hanging death of brother, Tom, ABC said. Kate, who was 14 at the time, was the one who discovered his body.