Ann Little was born Mary Brooks on a ranch near the town of Mount Shasta, California, she began appearing in a traveling stock theater group after graduating high school. After briefly relocating to San Francisco in the early 1910s, she made the transition to films; first appearing in one-reel Western shorts with actor and director Broncho Billy Anderson. Her first film appearance was in the 1911 release The Indian Maiden’s Lesson as a Native American named ‘Red Feather’. Little would often appear as Native American characters in many of her earliest films. By 1912, Ann Little was appearing regularly in Thomas H. Ince directed Western-themed serials, often as an “Indian princess” and usually starring opposite Francis Ford, Grace Cunard, Olive Tell, Jack Conway, Ethel Grandin, early American child actress Mildred Harris and notable early cowboy star Art Acord for Essanay Studios. Between 1911 and 1914, Little would appear in approximately sixty shorts, the overwhelming majority of them Westerns and many of them serials that ran in installments. Other notable co-stars of the era included Harold Lockwood, Jane Wolfe, William Worthington, Tom Chatterton, and actor/director Frank Borzage. Although possibly best recalled for her appearances in Westerns, Ann Little showed versatility as an actress by appearing in a number of well received roles in other dramatic genres and even comedies. Most notably among her dramatic roles was the early American cinematic Civil War serials directed by William J. Bauman and Thomas Ince. Another notable film of the period was the 1914 Ruth Ann Baldwin penned and Allan Dwan adapted epic Damon and Pythias, which included a cast of thousands of extras. While signed under contract to Universal Studios, she would make nearly six serials, most of them Western-themed one and two-reel dramas.

By 1917, Ann Little was signed to Paramount Pictures and often being paired with the highly successful actor Wallace Reid in a number of popular dramas and comedies, and while allegedly tired of being typecast as an actress of Western serials starred opposite cowboy actor Jack Hoxie in the popular 1919 serial Lightning Bryce. By the early 1920s however, Little would only take dramatic roles outside of the Western genre. Notable films of the period include the race-car adventure films The Roaring Road (1919) and Excuse My Dust (1920) with Wallace Reid, The Cradle of Courage with William S. Hart and the crime-drama The Greatest Menace (1923) opposite Wilfred Lucas. While still at the peak of her public popularity, Ann Little retired from the motion picture industry in the early 1930s. In her later years she managed the Chateau Marmont on the Sunset Strip but rarely spoke of her years in acting. Ann Little died at age 93, in Los Angeles, and was interred at the Forest Lawn Memorial Park, Glendale, California.