Born Leila Marie Koerber in Cobourg, Ontario to parents Alexander Rudolph Koerber (who was Austrian) and Anna Henderson. Being a rather overweight child, she spent a lot of time developing the defense mechanisms many overweight children become skilled at. The young Marie Dressler was able to hone her talents to make other people laugh, and at 14 years old she began her acting career in theatre. In 1892 she made her debut on Broadway. At first she hoped to make a career of singing light opera, but then gravitated to vaudeville.

During the early 1900s, she became a major vaudeville star. In 1902, she met fellow Canadian, Mack Sennett, and helped him get a job in the theater. In addition to her stage work, Dressler recorded for Edison Records in 1909 and 1910. After Sennett became the owner of his namesake motion picture studio, he convinced Dressler to star in his 1914 film Tillie's Punctured Romance opposite Sennett’s newly discovered actor, Charlie Chaplin. Dressler appeared in two more "Tillie" sequels plus other comedies until 1918 when she returned to work in vaudeville.

In 1919, during the Actors' Equity strike in New York city, the Chorus Equity Association was formed and voted Dressler its first president.

In 1927, she had been secretly blacklisted by the theater production companies due to her strong stance in a labor dispute. It would turn out to be another Canadian who gave her the opportunity to return to motion pictures, MGM studio boss Louis B. Mayer who called her "the most adored person ever to set foot in the Metro-Goldwyn-Mayer studio."

A robust, full-bodied woman of very plain features, Marie Dressler’s comedy films were very popular with the movie-going public and an equally lucrative investment for MGM. Although past sixty years of age, she quickly became Hollywood’s number one box office attraction and stayed on top for two straight years. In addition to her comedic genius and her natural elegance, she also demonstrated her considerable talents by taking on serious roles. For her starring portrayal in Min and Bill, co-starring Wallace Beery, she won the 1931 Academy Award for Best Actress. Dressler was nominated again for Best Actress for her 1932 role as Emma. With that film, Dressler demonstrated her profound generosity to other performers: Dressler personally insisted that her studio bosses cast a friend of hers, a then largely unknown young actor, Richard Cromwell, in the lead opposite her. It was a break that helped launch his career.

Dressler followed these successes with more hits in 1933 (like the wonderful comedy Dinner at Eight, in which she played an aging and poor former stage actress) and made the cover of the August 7, 1933 issue of Time magazine. However, her career came to an abrupt end when she was diagnosed with terminal cancer. MGM head Louis B. Mayer learned of Dressler's illness from her doctor and asked that she not be told. To keep her home, he ordered her not to travel on her vacation because he wanted to put her in a new film. Dressler was furious but complied.

In all, Marie Dressler appeared in more than 40 films but only achieved superstardom near the end of her life. Always seeing herself as physically unattractive, she wrote an autobiography, The Life Story of an Ugly Duckling.

Marie Dressler died in Santa Barbara, California and is interred in a crypt in the Great Mausoleum in the Forest Lawn Memorial Park Cemetery in Glendale, California.

She has a star on the Hollywood Walk of Fame at 1731 Vine Street. Each year the Marie Dressler Film Festival is held in her home town of Cobourg, Ontario.

More recently, another biography was published, entitled: Marie Dressler: The Unlikeliest Star by Ontario resident and writer Betty Lee.