He began his radio programs by announcing "Hello everybody, Lopez speaking!"[1] His theme song was "Nola", Felix Arndt's novelty ragtime piece of 1915, and Lopez became so identified with it that he occasionally satirized it. (His 1939 movie short for Vitaphone, Vincent Lopez and his Orchestra, features the entire band singing "Down with Nola".)

Lopez worked occasionally in feature films, notably The Big Broadcast (1932) and as a live-action feature in the Max Fleischer cartoon I Don't Want to Make History (1936). In 1940, he was one of the first bandleaders to work in Soundies movie musicals. He made additional Soundies in 1944.

Noted musicians who played in his band included Artie Shaw, Xavier Cugat, JIMMY Dorsey, Tommy Dorsey, Bob Effros, Mike Mosiello, Fred Lowery, Joe Tarto and Glenn Miller.[1] He also featured singers Keller Sisters and Lynch, Betty Hutton, and Marion Hutton. Lopez's longtime drummer was the irreverent Mike Riley, who popularized the novelty hit "The Music Goes Round and Round".

Lopez's flamboyant style of piano playing influenced such later musicians as Eddy Duchin and Liberace.

In 1941, Lopez's Orchestra began a residency at the Taft Hotel in Manhattan that would last 25 years.[1]

In the early 1950s, Lopez along with Gloria Parker hosted a radio program broadcast from the Taft Hotel called Shake the Maracas in which audience members competed for small prizes by playing maracas with the orchestra.