Set during the Great Depression, the film tells the story of Annie, an orphan from New York City who is taken in by America's richest billionaire Oliver Warbucks.
- Hugh Jackman as Oliver "Daddy" Warbucks, a billionaire businessman who opens his home to Annie.
- Bella Thorne as Annie, The spunky and optimistic 11 year old orphan who is looking for her birth parents.
- Keira Knightley as Grace Farrell, Oliver Warbucks' faithful secretary, who loves Annie from the start.
- Allison Janney as Miss Agatha Hannigan, The orphanage matron, disillusioned, she hates children, but is fond of alcoholic beverages.
- Paul Giamatti as Daniel "Rooster" Hannigan, an escaped convict and Miss Hannigan's younger brother.
- Margot Robbie as Lily St. Regis, Rooster's gold digging girlfriend.
- Michael Gambon as Drake, The butler at the Warbucks Mansion.
- Joey King as Molly, The youngest orphan (6) who is also Annie's best friend.
- Frank Welker as Sandy, An abandoned mixed–breed dog that Annie rescues him, he becomes her faithful companion.
- John Goodman as Franklin D. Roosevelt, the President of the United States, he aids Daddy Warbucks in the search for Annie's parents.
- TBA as Pepper, The bossiest orphan (12) Who likes to take control and is not very good friends with Annie.
- TBA as Duffy, The oldest orphan (13) Who often hangs around with Pepper but is friends with everyone.
- TBA as July, The quietest orphan (13) Who doesn't talk much but is mother-like to all the kids.
- TBA as Tessie, The crybaby orphan (10) Who is known for line "Oh my goodness".
- TBA as Kate, The shyest orphan (7) Who never really speaks but is friends with everyone.
- Conan O'Brien as Louis Brandeis, Associate Justice of the U.S. Supreme Court, he is called upon to assist in Annie's adoption.
- Rob Paulson as Bert Healy, a radio show host who agrees to broadcast Annie's search for her parents.
- Grey DeLisle, Tara Strong and Nika Futterman as The Boylan Sisters, Singers on the Bert Healy Show who hope to be famous someday.
- Dan Castellaneta as Lt. Ward, A policeman sent after Annie.
- Jeffrey Tambor as Harold Ickes, Cabinet Member who sings "Tomorrow" with Annie and Warbucks.
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