Russolo was born at Portogruaro, in the Veneto region, the son of an organist in the local cathedral and director of the Schola Cantorum of Latisana. His brothers (most notably Antonio) were also musicians.
Russolo moved to Milan in 1901, frequenting the Brera Academy, and took part to the restoration of Leonardo's Last Supper in Santa Maria delle Grazie. In his first works Russolo applied the divisionist techniques to a fantastic-symbolic view of subject related to the city or the industrial society.
An adherent of the Futurism movement, he worked closely with futurist Filippo Tommaso Marinetti.
On 11 March 1913 he published his noise music treatise The Art of Noises (L'arte dei rumori). He is one of the first theorist of electronic music. Russolo invented and built instruments including intonarumori ("intoners" or "noise machines"), to create "noises" for performance. Unfortunately, none of his original intonarumori survived World War II. Luigi's brother Antonio Russolo also composed futurist music.
In 1941-1942 Russolo started again to paint, with a new style that he defined "classic modernist".
He died at Cerro di Laveno (province of Varese) in 1947.
To honor the memory of the futurist composer, The Russolo-Pratella Foundation of Varese, Italy holds an annual international composition competition for electro-acoustic music. The Luigi Russolo Prize in Electro-Acoustic Music is one of the most prestigious awards in the field of electro-acoustic music.