O'Brien was born in Hollywood, California to actors George O'Brien and Marguerite Churchill. She began her studies with Milton Kestenbaum, former principal bass of the Pittsburgh Symphony under Fritz Reiner and member of the NBC Symphony under Arturo Toscanini; and with Herman Reinshagen, assistant-principal bass of the New York Philharmonic under Gustav Mahler and Arturo Toscanini at the University of California, Los Angeles. She continued her studies at the Juilliard School in New York City with Frederick Zimmermann, assistant principal double bass of the New York Philharmonic for many of his 36 years there. [citation needed] O'Brien attended the Music Academy of the West summer conservatory in 1952,1953,1954, and 1955.[2]
Before joining the New York Philharmonic, O'Brien performed with the New York City Ballet, the Metropolitan Opera, and the American Symphony Orchestra (under Leopold Stokowski, under whom she played the double bass solo as principal bass in the U.S. premiere of Alberto Ginastera's Variaciones Concertantes, in 1962). She performed at the Marlboro Music Festival in the 1960s where she made recordings with Pablo Casals and gave the premiere of Gunther Schuller's Quartet for Double Basses, which was later recorded with Alvin Brehm, Robert Gladstone and Frederick Zimmermann.
She formerly taught at YMHA, the Estherwood Summer Musical Festival, and the Institute de Haute Etudes Musicales in Montreux, Switzerland. Orin O'Brien has given masterclasses at the Peabody Institute, the Tanglewood Festival, New England Conservatory, and Yale University. [citation needed] Her career is depicted in the 2023 short documentary film The Only Girl In The Orchestra, directed by Orin's niece, Molly O'Brien.