Like many stage actors of her era, she expressed a distaste for films and resisted the offers she received during the 1920s. Finally, she relented and made her film début in Night Angel (1931), but her scenes were cut before the film's release. Her official film début came in The House of Trent (1933), and Quality Street (1937) was her first role of note. She made no cinematic films during the 1940s, but expressed a willingness to participate in the new medium of television, starring in a television production of Blithe Spirit in 1946. During the 1950s, she appeared more frequently in television than she did in film in such series as Robert Montgomery Presents, Alfred Hitchcock Presents, and The Donna Reed Show. She played the character Hortense in the episode "Where's There's a Will" (August 30, 1960) on the ABC sitcom The Real McCoys starring Walter Brennan. Her few films from that period include The Glass Slipper (1955), The Swan (1956), and 23 Paces to Baker Street (1956).

Her other film credits include Darby O'Gill and the Little People (1959), The Misfits (1961), The Magic Sword (1962), The Notorious Landlady (1962), Dead Ringer (1964), Camelot (1967) and The Producers (1967). She later denigrated the last film, saying she could not imagine why she had done it except for the money.

Her other work for television included guest roles in Dennis the Menace, The Twilight Zone, Thriller, Dr. Kildare, The Man from U.N.C.L.E., The Name of the Game, Bewitched, Batman, Love, American Style, Cannon, Police Story, The FBI, and the last episode of Perry Mason, titled "The Case of the Final Fade-Out", in which she plays an aging actress who ends up as a second defendant. Estelle Winwood also appeared in Barnaby Jones; episode titled "Murder in the Doll's House" (03/25/1973).

Winwood's final film appearance, at age 92 in Murder by Death (1976), was as Elsa Lanchester's character's ancient nursemaid. In this film, she joined other veteran actors spoofing some of the most popular detective characters in murder mysteries on film and television (Dick and Dora Charleston, Jessica Marbles, etc.). When she took on her final major television role in a 1979 episode of Quincy, she officially became, at age 96, the oldest actor working in the U.S., narrowly beating fellow British actress Ethel Griffies. She continued making appearances until she was 100 years old. When she died at age 101, she was the oldest member in the history of the Screen Actors Guild.