Reports say O'Donnell will shoot her new show at Harpo's facilities.
O'Donnell's show will air on the Oprah Winfrey Network.
The final original episode of Winfrey's show is scheduled to air May 25. Winfrey opened the studios in 1990.
"I'm delighted to welcome Rosie to the studio I've called home for so many years," Winfrey said in a statement.
The network announced last summer that O'Donnell would return to television with a one-hour talk show to air on OWN. The network said at the time that the show would be based in New York.
"I can't wait to do my show from Chicago," O'Donnell said in a statement. "It's a dream come true ... beyond the beyond."
O'Donnell previously hosted "The Rosie O'Donnell Show" from 1996 to 2002, earning six daytime Emmy awards. O'Donnell also spent time on "The View."
Harpo Studios presidents Erik Logan and Sheri Salata called the announcement "an exciting new chapter" for the company.
The Associated Press contributed to this report.