Frederick was born Pauline Beatrice Libbey (later changed to Libby) in Boston in 1883 (some sources state 1884 or 1885), the only child of Richard O. and Loretta C. Libbey. Her father worked as a yardmaster for the Old Colony Railroad before becoming a salesman. Her parents separated when she was toddler and Fredrick was raised primarily by her mother to whom she remained close for the remainder of her life (her parents divorced around 1897). As a girl, she was fascinated with show business, and determined early to place her goals in the direction of the theater. She studied acting, singing and dancing at Miss Blachard's Finishing School in Boston where she later graduated.
Her father, however, discouraged her ambitions to be an actress and encouraged her to become an elocution teacher. After pursuing a career as an actress, her father disinherited her (he died in 1922). Due to her father's attitude towards her acting career, Pauline adopted the surname "Frederick" as her stage name. She legally changed her name to Pauline Frederick in 1908.
She made her stage debut at the age of 17 as a chorus girl in the farce The Rogers Brothers At Harvard, but was fired shortly thereafter. She won other small roles on the stage before being discovered by illustrator Harrison Fisher who called her "the purest American beauty." With Fisher's help, she landed more substantial stage roles. Nicknamed "The Girl With the Topaz Eyes", Fredrick was cast in the lead roles in the touring productions of The Little Gray Lady and The Girl in White, in 1906. She briefly retired from acting after her first marriage in 1909, but returned to the stage in January 1913 in Joseph and His Brethren.
A well-known stage star, Frederick was already in her 30s when she made her film debut in 1915. In March 1927, she won some of her best reviews when she appeared in the play Madame X in London. Frederick was able to make a successful transition to "talkies" in 1929, and was cast as Joan Crawford's mother in This Modern Age (1931). Frederick did not like acting in sound films and returned to Broadway in 1932 in When the Bough Breaks. She would continue the remainder of her career appearing in films and also touring in stage productions in the United States, Europe and Australia.
Frederick's personal life was beset with marital and financial problems. Despite having reportedly made a million dollars for her work in silent films, Frederick filed for bankruptcy in 1933.
Frederick was married five times. Her first marriage was to architect Frank Mills Andrews, whom she married in 1909. After the marriage, Frederick retired from acting but returned after divorcing Andrews in 1913. She married her second husband, playwright Willard Mack, on September 27, 1917. They divorced in August 1920. Her third marriage was to Dr. Charles A. Rutherford, a physician, whom she married in Santa Ana, California in 1922. Fredrick filed for divorce in December 1924. Their divorce was finalized on January 6, 1925. Frederick's married her fourth husband, hotel owner Hugh Chisom Leighton, on April 20, 1930 in New York City. Leighton had the marriage annulled in December 1930 claiming that he was Frederick's husband "in name only".
Frederick married for the fifth and final time to United States Army Colonel James A. Marmon in January 1934. They remained married until Marmon's death on December 4, 1934.
On January 17, 1936, Frederick underwent emergency surgery on her abdomen. Her health steadily declined afterwards which limited her ability to work. She was dealt a further blow when her mother died in 1937.
On September 16, 1938, Frederick suffered an asthma attack. She suffered a second, fatal asthma attack while she was recuperating at her aunt's home in Beverly Hills. According to her wishes, a private funeral was held on September 23 in Hollywood, after which she was buried at Grand View Memorial Park Cemetery.
For her contribution to the motion picture industry, Pauline Frederick has a star on the Hollywood Walk of Fame at 7000 Hollywood Boulevard.