Lucille Carlisle was born Ida Lucille White in Galesburg, Illinois. After her father abandoned the family her mother opened a boarding house in Spokane, Washington. At the age of sixteen Lucille was briefly married. Soon after she she won a beauty contest organized by Photoplay Magazine. She moved to New York City and began her career on Broadway as Lucille Zintheo. Later she changed her stage name Lucille Carlisle. In 1918 she was signed by Vitagraph Pictures and was cast in the Larry Semon comedy Boodle and Bandits. Larry and Lucille would make more than a twenty movies together including The Simple Life and A Pair of Kings. They became a popular onscreen team while off screen they had a tempestuous romance. Lucille was unhappy with the shape of her nose and underwent numerous plastic surgeries.

In 1922 she and Larry were secretly married. Later that year Lucille suffered a nervous breakdown. She recovered but her marriage to Larry ended in divorce. In 1923 she auditioned for the lead in The Hunchback of Notre Dame but Patsy Ruth Miller got the part. Lucille developed a drinking problem and was often under a doctor's care for her nerves. She decided to stop acting and married businessman Leland H. Millikin in 1930. Lucille, who never had children, adopted her niece when her sister was unable to raise her. During World War 2 she made several radio appearances. Lucille died on October 19, 1958 due to a liver disorder. She was buried at Forest Lawn Memorial Park in Glendale, California.