Brian was dubbed “The Sweetest Girl in Pictures.” On loan-out to MGM, she played a college belle, Mary Abbott, opposite William Haines and Jack Pickford in Brown of Harvard (1926). She was named one of the WAMPAS Baby Stars in 1926, along with Mary Astor, Dolores Costello, Joan Crawford, Dolores del Río, Janet Gaynor, and Fay Wray.

During her years at Paramount, Brian appeared in more than 40 movies as the lead, the ingenue or co-star. She worked with Brenon again in 1926 when she played Isabel in P. C. Wren’s Beau Geste starring Ronald Colman. That same year she made Behind the Front and Harold Teen. In 1928, she played ingenue Alice Deane in Forgotten Faces opposite Clive Brook, her sacrificing father, with Olga Baclanova as her vixen mother and William Powell as Froggy. Forgotten Faces is preserved in the Library of Congress.

After her contract with Paramount ended in 1932, Brian decided to freelance, which was unusual in a period when multi-year contracts with one studio were common.. That same year, she appeared on the vaudeville stage at New York’s Palace Theatre. Also in the same year, she starred in Manhattan Tower.

In 1936, she went to England and made three movies, including The Amazing Quest of Ernest Bliss in which she starred opposite Cary Grant, to whom she became engaged at one stage.

When World War II hit in 1941, Brian began traveling to entertain the troops, ending up spending most of the war years traveling the world with the U.S.O., and entertaining servicemen from the South Pacific to Europe, including Italy and North Africa. Commenting on those events that had occurred over fifty years ago, she said in 1996,

She played in the stage comedy Mary Had a Little… in the 1951 in Melbourne, Australia, co-starring with John Hubbard.

Like many “older” actresses, during the 1950s Brian created a career for herself in television. Perhaps her most notable role was playing the title character’s mother in Meet Corliss Archer in 1954. .

In 1960, Brian was inducted into the Hollywood Walk of Fame with a motion pictures star located at 1559 Vine Street.

She died of natural causes on December 30, 2002 at a retirement home in Del Mar, California at the age of 96. She is interred in the Eternal Love Section, Lot 4134, Space 2, Forest Lawn – Hollywood Hills Cemetery, Los Angeles, overlooking Burbank.