Glaum began her acting career in stock and stage productions. She was in the cast of Crucifixus, a Passion play, which opened on November 12, 1907, at the Gamut Auditorium in Los Angeles, before a good-sized audience. In early June, 1908, she appeared in the play How Baxter Butted In, a melodramatic comedy at the Los Angeles Theatre. The cast included Lulu Warrenton and a number of others. Glaum then toured as an ingenue with a road show in Why Girls Leave Home. She earned $25 a week and furnished her own gowns, which she made herself. After reaching Chicago, she played ingenues in the Imperial Stock Company there for a year and a half, appearing in The Lion and the Mouse and The Squaw Man, among other plays. While performing in a summer stock engagement in Toledo, she created the ingenue role in Officer 666. Its playwright, Augustin MacHugh, her stage director in Toledo, tried it out there before Broadway ever saw the successful farce.
Upon the death of her younger sister, Margaret, in June 1911, Glaum resigned and returned home to Los Angeles. On July 29, the Los Angeles Times read, "Louise Glaum, ingenue, who made her professional start here a few years ago, is at home on a short visit. Of late she has been playing in Chicago.
Her mother wanted her to remain, but the desire to return to the stage possessed her. She compromised, however; while acting as the ingenue in a local theatre company, she began making the rounds of the movie studios.
She played Mary Thorne in the drama The Goddess of Lost Lake (1918), which she also co-produced through her own production company, the Louise Glaum Organization. It is the story of a young woman who is a quarter Native American and decides to pretend she is a full-blooded Indian princess when she visits her father's rustic cabin after completing college in the East. Glaum then began working with J. Parker Read Jr. Productions, which she later described as J. Parker Read, Jr.'s unit as a subsidiary producing company for Thomas Ince. She signed a four year contract, with a salary starting at $2000 a week and increasing to $4000, and some of the features she starred in for that company were as Mignon in Sahara (1919), a big financial success that was written especially for the star by C. Gardner Sullivan, with the production supervised by Allan Dwan; the dual role as Princess Sonia and as her daughter, Sonia, in the crime/thriller The Lone Wolf's Daughter (1919); as Adrienne Renault in the provocatively titled Sex (1920), the story of a New York cabaret star who uses her sex appeal to end a marriage then leaves her lover for a wealthier prospect only to have her selfish way of life come back to haunt her; and the title role in The Leopard Woman (1920), a secret agent adventure set in the jungles of Africa.
In 1920, Glaum was maintaining her own household in Los Angeles, with a married couple, housekeeper and caretaker, and a gardener. After starring in the role as Grace Merrill in the drama Greater Than Love (1921), directed by Fred Niblo, she retired from the screen.
On March 16, 1925, she filed suit in the Supreme Court of New York against producer J. Parker Read, Jr., for $103,000 and asked for an attachment against money owed him by various film distributors in New York City. The complaint stated she was starred in several pictures under Read's direction, and on December 23, 1921, he made a promissory note to her for the money, payable in four instalments. Nothing was paid, however, and in the Fall of 1923, according to Glaum, he went to Paris without paying her. According to her attorney, Read's departure took the form of a flight and he had disguised himself as a stoker on a ship.
She then sued the estate of Thomas H. Ince, Read's partner, stating that Read was insolvent and asking for the $103,000 plus $290,000 for breach of contract. The Appellate Division, however, decided that she could not prosecute a suit in the state against the executors under the will of Ince on the grounds that the New York courts had no jurisdiction over the executors, who were appointed in California, in which state Ince was a resident at the time he died in November 1924. She then filed suit in California, but a copy of the contract was not attached. By the time that arrived, the time had elapsed in which she was legally entitled to make a claim against the Ince estate and the court dismissed the suit on technicalities.
She made one screen comeback. Signing a contract with Associated Exhibitors, she played the role as Nina Olmstead in the Henri Diamant-Berger directed drama Fifty-Fifty (1925) starring Hope Hampton and Lionel Barrymore.
Glaum then stayed away from Los Angeles, for over three years as she headlined on the big-time vaudeville circuit in the East. She did a tour of Leow's Theatres in two dramatic playlets. One of them was The Sins of Julia Boyd by Paul Girard Smith. The other was The Web, which Glaum wrote herself. She was the only character in the one person show, putting over the argument of the piece chiefly by a telephone conversation.
When she returned to Los Angeles, with her husband and business manager, Zack Harris, to visit her family and friends, they decided to stage the play Trial Marriage at the Egan Theatre, with Glaum in the starring role. When asked by a reporter for the Times whether she would be doing any picture work, she said she had not thought of it, but acknowledged that she was interested in talking pictures.
On November 16, 1928, Glaum opened in Trial Marriage, the story of a woman who wants to test the suitability of her prospective mate and herself to each other without the benefit of wedlock before they make it permanent. Although she received good reviews, the play did not fare so well.
She and Harris lived at 2282 Cambridge Street in Los Angeles, in 1930. Glaum continued to act on the stage and also became a drama instructor, opening and appearing in her own theatre, the Louise Glaum Playhouse, in Los Angeles in the mid 1930s.
She was also a busy clubwoman over the following three decades. She served as president of the Matinee Musical Club for many years and served as state president of the California Federation of Music Clubs.
Louise Glaum died at age 82 of pneumonia in Los Angeles. She is interred in Angelus-Rosedale Cemetery, along with her second husband and others of her family. She has a star on the Hollywood Walk of Fame for her work in motion pictures at 6834 Hollywood Boulevard, Hollywood.