Lyles was born in Jackson, Tennessee, and attended Fisk University in Nashville as a medical student.

From 1905, Miller and Lyles were hired by impresario Robert T. Motts[1] to be resident playwrights with the Pekin Theater Stock Company in Chicago.

They performed with the company in blackface, and in the show The Colored Aristocrats introduced the characters Steve Jenkins (Miller) and Sam Peck (Lyles), with which they would be associated for many years.

They developed comedy devices later copied by others, such as a prizefighting routine which contrasted Miller's height and Lyles' short stature; completing each other's sentences; and "mutilatin'" the language in their phraseology.

[2] Miller and Lyles continued to work together for several years writing and performing in Broadway shows including Runnin' Wild – one of the first shows to popularize the Charleston, in 1923, with a score by James P. Johnson – Rang Tang (1927), which they co-directed; and Keep Shuffling (1928) which featured music by Fats Waller.