Born in Pittsburgh, Pennsylvania, Wilson's family moved to Alabama when she was still very young. After becoming a schoolteacher, Wilson moved to California when she won a beauty contest put on by Universal Studios in 1915. Upon arriving in Hollywood Lois secured a small part in The Dumb Girl of Portici which starred the ballerina Anna Pavlova.
After appearing in several films at various studios, Wilson settled in at Paramount Pictures in 1919, where she remained until 1927. She was a WAMPAS Baby Star of 1922, and all told, appeared in 150 movies. Lois' most recognized screen portrayals are Molly Wingate in The Covered Wagon (1923) and Daisy Buchanan in the silent film version of The Great Gatsby (1926). She acted opposite such leading male stars of her era as Rudolph Valentino and John Gilbert.
Wilson demonstrated a wide range of talent, playing both romantic leads and character parts. Despite making a successful transition to sound, Wilson was dissatisfied with the roles she received in the 1930s and she soon retired in 1941, making only five films after 1939. Lois ventured to Broadway and television following her final role in The Girl From Jones Beach (1947) with Ronald Reagan. Wilson played in the network soap operas The Guiding Light in (1952) and The Edge of Night. She portrayed featured character roles.
She was once described as having a screen image of "the soft, marrying kind of woman". However, in real life she never married. Lois was chosen by Paramount Pictures to represent the motion picture industry at the British Empire Exposition of 1924. She was described as "a typical example of the American girl in character, culture and beauty".