The Oprah Winfrey Network announced Thursday that the comedian and actor will appear on the Oct. 10 premiere of "The Rosie Show."
O'Donnell has said she's fascinated with Brand and called him a genius. She previously said she would love to have him as her first guest.
The show will air on the Oprah Winfrey Network, which promises Brand will be "one of many notable celebrities" during the show's first two weeks.
O'Donnell will tape in Chicago's Harpo Studios, former home of "The Oprah Winfrey Show" until it ended in May after 25 years.