He was born aboard a ship as his parents emigrated from Italy and trained to be a classical violinist from an early age. He met Eddie Lang in 1913 while attending school in Philadelphia and started a local group with him three years later. The two would go on to play and record with each other frequently up until Lang's death in 1933.
Venuti played briefly with Red Nichols, toured with Jean Goldkette and played in the orchestra of many Broadway shows. He co-led a band with Eddie Lang off and on through most of the 1920's, that included Jimmy Dorsey, Red Nichols and Frank Signorelli of the Original Dixieland Jass Band.
In 1929 he joined the Paul Whiteman Orchestra but was injured in an auto accident; he was able to re-join the band in 1930. Venuti was able to keep working as a musician the rest of his life. He enjoyed a resurgence of interest in the 1970s.