He found work as a singer at various lodge halls, on ferry boat lounges, in saloons, and even between bouts at the athletic clubs.

In this way, the young Edwards would often sit in a balcony seat, and then stand and repeat a song that vaudeville stars such as Maggie Cline, Lottie Gilson or Emma Carus had just sung.

In 1896, Edwards was 17 years old and appearing at Johnny Palmer's Gaiety Saloon in Brooklyn, when James Hyde, a vaudeville agent, saw him performing.

While entertaining soldiers at Camp Black, during the Spanish–American War, Edwards met lyricist Will Cobb, and they formed "Words and Music", a partnership that lasted for many years.

He founded the Gus Edwards Music Hall in New York, and also his own publishing company, then produced special subjects for films, and returned to vaudeville between 1930 and 1937, finally retiring in 1939.

His other popular-song compositions include "Meet Me Under the Wisteria", "By the Light of the Silvery Moon", "I Can't Tell You Why I Love You but I Do", "Goodbye, Little Girl, Goodbye", "I Just Can't Make My Eyes Behave", "I'll Be With You When the Roses Bloom Again", "He's My Pal", "Way Down Yonder in the Cornfield", "In Zanzibar", "If a Girl Like You Loved a Boy Like Me", "Jimmy Valentine", "If I Were a Millionaire", "Laddie Boy" and "In My Merry Oldsmobile".

Bing Crosby played Edwards in a fictionalized version of his life in the 1939 film The Star Maker, directed by Roy Del Ruth.