The comedian, who portrayed Doris Murphy in the original film in 1992, announced that she would be a guest star while appearing on podcast Everything Iconic with Danny Pellegrino.
Amazon's version will follow a generation of women who dreamed of playing baseball while exploring race and sexuality. Abbi Jacobson (Broad City) co-created the series with Will Graham, with the duo additionally serving as executive producers.
O'Donnell told Pellegrino that she will portray a bartender at a gay bar in the series.
"She called me and said, 'Ro, would you do it? And I said, 'In a minute.' Then she sent me the pilot that she did and it was just really beautiful," O'Donnell recalled about speaking with Jacobson.
Jacobson also stars on the series alongside Nick Offerman, Chanté Adams, D'Arcy Carden, Gbemisola Ikumelo, Kelly McCormack, Roberta Colindrez and Priscilla Delgado.
O'Donnell recently guest starred on Starz comedy Run the World and will guest star on the upcoming second season of The L Word: Generation Q.