One of her earliest appearances was in George Bernard Shaw's The Shewing-Up of Blanco Posnet in which she played the part of a swaggering American ranch girl.

The production played in Dublin as well as in New York, opening 20 November 1911 at the Maxine Elliott Theatre, marking O'Connor's American debut.

A review of the New York performances of The Fake recounts details of the plot, but then mentions two players of more than ordinary excellence.

He does not respond at all and the longing, the pathos of this servant girl when she has exhausted her charms and receives no encouragement, is the very epitome of what careful character portrayal should be.

Miss O'Connor is on the stage for only this single act, but in that short space of time she registers an indelible impression.

Returning to London, she played in The Ring o' Bells (November 1925), Autumn Fire (March 1926), Distinguished Villa (May 1926),[2] and Quicksands of Youth (July 1926).

[8] When Autumn Fire toured the U.S., opening first in Providence, Rhode Island, a critic wrote: "Una O'Connor, who plays Ellen Keegan, the poor drudge of a daughter, bitter against life and love, does fine work.

[10] Her luck changed when she was chosen by Noël Coward to appear in Cavalcade at the Theatre Royal, Drury Lane in 1933.

Among O'Connor's most successful and best remembered roles are her comic performances in James Whale's The Invisible Man (1933) as the publican's wife, and in Bride of Frankenstein (1935) as the Baron's housekeeper.

Feeling homesick, in 1937 she returned to London for twelve months in the hope of finding a good part but found nothing that interested her.

[10] Her film career continued with roles in Michael Curtiz's The Adventures of Robin Hood (1938) and The Sea Hawk (1940); and in Leo McCarey's The Bells of St. Mary's (1944).

She appeared in stage productions in supporting roles and achieved an outstanding success in the role of Janet McKenzie, the nearly deaf housemaid, in Agatha Christie's Witness for the Prosecution at Henry Miller's Theatre on Broadway from 1954 to 1956; she also appeared in the film version in 1957, directed by Billy Wilder.

[13] Observing many actors disliked television work, O'Connor took the opposite view in liking the medium it because it allowed her to play many parts.

She could take a very small part, but out of the paltry lines at her disposal, create a real flesh-and-blood creature, with a complete and credible life of its own.

[2] She died, having never married nor had children, in New York City from heart disease, aged 78, on 4 February 1959 at the Mary Manning Walsh Home.