Keppard was born in the Creole of Color community of downtown New Orleans, Louisiana. His older brother Louis Keppard was also a professional musician. Freddie played violin, mandolin, and accordion before switching to cornet. After playing with the Olympia Orchestra he joined Frankie Dusen's Eagle Band, taking the place recently vacated by Buddy Bolden. Soon after Bolden was off the music scene Keppard was proclaimed "King Keppard" as the city's top horn player.
About 1914 Joe Oliver won a musical "cutting contest" and claimed Keppard's crown; soon after Keppard accepted an offer to join Bill Johnson's band in Los Angeles, California.
Johnson and Keppard's band became the Original Creole Orchestra which toured the Vaudeville circuit, giving other parts of the USA a first taste of the music that was not yet known as "jazz". While playing a successful engagement in New York City in 1915 the band was offered a chance to record for the Victor Talking Machine Company. In retrospect this would probably have been the first jazz recording. An often repeated story says that Keppard didn't want to record because then everyone else could "steal his stuff". The reminiscences of the other members of the Creole Orchestra reveal that another factor was that the Victor representative had asked them to make a "test recording" with out pay, and the band balked, fearing it was a ploy to have them make records without being paid.
About 1917 Keppard settled in Chicago, which would remain his home (except for breifly going to the East Coast to work with Tim Brymn's band about 1920). Keppard worked in Chicago both as a soloist and with the bands of Jimmie Noone, Johnny Dodds, Erskine Tate, Doc Cooke (for several years), Don Pasquall, and Lil Hardin Armstrong.
Keppard made all his known recordings in Chicago from 1924 to 1927. The only recordings he is certainly on are 3 sides under his own name ("Freddie Keppard's Jazz Cardinals") and a dozen with Doc Cooke's Orchestra, most of which are heavily arranged and with Keppard on second trumpet. There are a few other recordings on which he plausibly may appear, and a great many more that are sometimes dubiously attributed to him. Keppard was widely imitated both in New Orleans and Chicago.
Many of his contemporaries said that either Keppard was past his prime when he recorded or that his recordings do not do him justice. None the less, carefull listening to the sides which he is undoubtably on reveal Keppard to be a technically very proficient player and an adventurous improviser, albeit in a rather archaic style compared to later jazz.
Keppard's style is much more raggy compared to Oliver's blues tinged style. While Oliver had more admirers, to some extent preference was a matter of taste; Jelly Roll Morton, Lil Hardin Armstrong, and Wellman Braud all thought Keppard superior to Oliver.
Several musicians with clear memories of Buddy Bolden said that Freddie Keppard sounded the most like Bolden of anyone who recorded.
Keppard suffered from alcoholism and tuberculosis in his final years, and died largely forgotten in Chicago.