Clarence Edouard Muse was born on October 7 (or 14, date disputed), 1889, to Alexander Muse and Mary Sales in Baltimore, Maryland. He wed Frieda Belle Moore in 1907, but shortly after the birth of their first son in 1910 the marriage dissolved. Muse was one of the first black students to graduate from the Dickinson School of Law in Carlisle, Pennsylvania in 1911. He never pursued a career in law, however, because of the lack of opportunities for African Americans. However, Muse requested "...that he be addressed as Dr. Muse," according to Hal Erickson, who writes for All Movie Biographies.

Muse was a community activist and worked to better the careers of black actors through participating in the Black theater movement of the 1920s. Muse, who had participated in choral groups while in college, focused his attention on an acting career in show business. However, he did not limit himself to movie acting. He composed songs, wrote plays, directed movies, and made regular appearances on the weekly television version of Casablanca.

By 1914, he married Ophelia, whose maiden name is unknown, and they performed along the East Coast together before settling in Harlem, New York. At the Franklin Theatre, along with their partner Willard Pugh, they established the Muse and Pugh Stock Company, which was later known as the Crescent Players. Their company was briefly moved to the Crescent Theatre, where Muse and his wife starred in the play Another Man's Wife. They then moved their company to the Lincoln Theatre. It merged with a progressive group known as the Lincoln Players. Later they joined the Lafayette Players in 1916. With this new group, Muse became the leading dramatic actor and starred in many plays.

In 1920, the members of the Lafayette Players supported Muse when he became one of the founding directors of a black independent film company, the Delsarte Film Corporation, in New York City. Muse and his wife had two children together, but their marriage did not last. The year 1922 marked their last performance together.

Muse soon ventured to Chicago, Illinois, and he became associated with the Royal Gardens Theatre. He went on to produce and direct shows from 1922 until 1929, when he accepted the invitation to Hollywood the Fox Film Corporation sent to him to portray a leading character in the film, Hearts of Dixie. This was during the transition from silent films to talking films, and Hearts of Dixie was the second movie to ever have talking. Muse did not believe that these new talking movies would last, which led him to ask for what would have been considered an extremely high paying weekly salary of $1,250 with a 12-month contract, as well as round-trip tickets for his family to travel with him. His request was honored, and he resided in Hollywood for the remainder of his career.

Muse married Willabella Marchbanks at an undocumented time in history. Together they had one child, but they divorced by 1949. His fourth and final marriage was to Irene Claire Kellman in 1954.

Muse appeared in 218 movies throughout his lifetime, which were all filmed during his 50-year stay in Hollywood. Among the most well-known of these movies are: Broken Strings, Way Down South, and The Black Stallion. He was inducted into the Black Filmmakers Hall of Fame in 1973.

Similar to other African-Americans in this time, Muse had difficulty getting past the stereotypical roles of the accommodating butler-type character portrayal. He overcomed these obstacles and starred as a concert violinist in the film Broken Strings, a remake of The Jazz Singer meant primarily for all-Black audiences. Muse also appeaered in non-submissive roles for mainstream films occasionally. One such role was The Invisible Ghost when Muse portrayed an opinionated butler in 1941. He is quoted harshly speaking to a white female servant, voicing aloud, "You old fool!" This was a significant moment for the Black community. It captured the struggle of changing times when Blacks were fighting for their equality and gaining momentum.

Muse was also a composer of plays and musicals, although he was known more widely as an actor. He starred in and coauthored the script, screenplay, and songs for Way Down South, a Bobby Breen musical, with Langston Hughes in 1939. He also composed what became Louis Armstrong's theme song, "When It's Sleepy Time Down South." This song was co-written with the Ren?? brothers from New Orleans, Louisiana, who became popular in the age of R&B music.

In the later years of his life, Muse lived in Perris Valley, California. He attended the city council meetings and demanded that his concerns be addressed. Muse's concerns included the community arts and senior-citizen issues. His motto, which writer Joe Vargo for the Press-Enterprise quotes, shows his high self-esteem: "In my entire life, I have never met a man or a woman with enough intelligence to insult me."

When Muse was in his early 70s, he began the Perris Arts Festival. Children were important to Muse, and he began this festival as an opportunity for them to perform in the arts and music. Resident of Perris Valley Virniecia Davis was quoted by Joe Vargo for the Press-Enterprise, saying, "He made you realize that you can accomplish goals and that the impossible is not impossible. He seemed to be everywhere in the community. He really loved kids and wanted them to succeed." Davis was a Perris High School student when had she met Muse, and he had encouraged her to continue her education.

On September 22, 1979, at his ranch in Riverside County, Muse suffered a stroke and was admitted into the Community Hospital of Perris Valley. Muse died at the age of 90 on Saturday, October 13, 1979, of a cerebral hemorrhage. Shortly after his death, his last film, The Black Stallion, was released.