Of Portuguese ancestry, Louise Fazenda was born in Lafayette, Indiana. Her father, Joseph Fazenda, was a merchandise broker. After moving west Louise attended Los Angeles High School and St. Mary’s Convent. Before trying motion pictures, she worked for a dentist, a candy store owner, and a tax collector and on stage. Louise Fazenda got her start in comedy shorts as early as 1913 with Joker Studios, frequently appearing with Max Asher and Bobby Vernon. She was soon recruited for Mack Sennett’s troupe at Keystone Studios. As with many Keystone actors, Fazenda’s star soon grew larger than Sennett was willing to pay for, and she left Sennett in the early 1920s for better roles and more money. She took a break from making motion pictures in 1921–1922 in order to try vaudeville. Fazenda appeared in a variety of shorts and feature-length films throughout the decade. By the advent of sound pictures, Fazenda was a highly paid actress, making movies for nearly all of the big studios. Fazenda continued through the 1930s, appearing mostly in musicals and comedies. Her skill was in performing character roles. She played such diverse parts as a fussy old maid and a lady blacksmith. She was once accurately described as a plain-looking woman but a highly gifted character comedienne. In 1927, Louise Fazenda married noted Warner Bros. producer Hal B. Wallis, a union which lasted until her death. They had one son, Brent, who became a psychologist in Florida. The Old Maid, in 1939, was her last of nearly 300 movie appearances. She spent the remainder of her years enjoying life as an art collector until her death caused by a cerebral hemorrhage. Hal Wallis was in Hawaii making a film and left immediately for home. She was interred at the Inglewood Park Cemetery in Inglewood, California. Louise Fazenda has a star on the Hollywood Walk of Fame at 6801 Hollywood Blvd.

In 1954, Fazenda read about a woman who died in a car accident. She paid the entire hospital bill of her daughter, who was injured in the wreck. She subsidized the studies of a law student who was contemplating leaving school when his wife became pregnant. At the UCLA Medical Center she helped to feed young children, before she rocked and sang them to sleep. Actress Laura La Plante witnessed her charitable efforts. LaPlante described Fazenda helping children and poor people. One child refused to eat. The actress reportedly went back and forth to the hospital from her home, making various dishes, until she was successful, and the youth regained his health. Among the children she helped there was one Edward Bunker, who described what had happened in his autobiographical The Education of a Felon.