After her showing in the beauty contest, she was given an audition by Paramount Pictures and cast by director Herbert Brenon as Wendy Darling in his silent movie version of J.M.

Brian played Fancy Vanhern, daughter of Percy Marmont, in Brenon's The Street of Forgotten Men (1925), which had newcomer Louise Brooks in an uncredited role as a moll.

On loan-out to MGM, she played a college belle, Mary Abbott, opposite William Haines and Jack Pickford in Brown of Harvard (1926).

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.

After successfully making the transition to sound, she co-starred with Gary Cooper, Walter Huston and Richard Arlen in The Virginian (1929), her first all-sound movie.

In it, she played a spirited frontier heroine, schoolmarm Molly Stark Wood, who was the love interest of the Virginian (Cooper).

Brian co-starred in several hits during the 1930s, including her role as Gwen Cavendish in George Cukor’s comedy The Royal Family of Broadway (1930) with Ina Claire and Fredric March, as herself in Paramount's all-star revue Paramount on Parade (1930), as Peggy Grant in Lewis Milestone’s comedy The Front Page (1931) with Adolphe Menjou and Pat O'Brien.

Other movie roles include Murial Ross, aka Murial Rossi, in Shadows of Sing Sing (1933), in which she received top billing; Gloria Van Dayham in College Rhythm (1934); Yvette Lamartine in Charlie Chan in Paris (1935); Hope Wolfinger, W.C. Fields’s daughter, in Man on the Flying Trapeze (1935); Sally Barnaby in Spendthrift (1936); and Doris in Navy Blues (1937), in which she received top billing.

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 for a time.

Her final film of the 1930s was Affairs of Cappy Ricks, although she auditioned for the part that ultimately went to Janet Gaynor in A Star is Born.

Colonel Paul Tibbets, who was the pilot and the officer in charge [of dropping the bomb] took Charlie and me on the plane the next day, and nobody had been allowed in that encampment.

After retiring from movies for good, she devoted herself to her husband's career; Tomasini worked as a film editor for Alfred Hitchcock on Rear Window (1954) and Psycho (1960).