Memphis is well known for its cultural contributions to the identity of the American south. Many renowned musicians grew up in and around the Memphis and Mississippi Delta. These included such musical greats as Elvis Presley, Jerry Lee Lewis, Muddy Waters, Carl Perkins, Johnny Cash, Robert Johnson, W. C. Handy, B.B. King, Howlin' Wolf, Isaac Hayes, Booker T. Jones, Al Green, and many others.

Beale Street in Downtown Memphis was a significant location in the development of the blues, and it remains a mecca for live performances today. Johnny Cash, Elvis Presley, Issac Hayes and B. B. King all got their start in Memphis in the 1950s. The Stax record label, founded in 1957 as Satellite Records, was originally based in Memphis and was a major factor in the creation of the Southern soul and Memphis soul music styles, also releasing gospel, funk, jazz, and blues recordings. Memphis is also noted for its influence on the power pop musical genre in the 1970s, with notable bands and musicians including Big Star, Chris Bell, Alex Chilton, Tommy Hoehn, The Scruffs, and Prix. More recently, Goner Records has released punk and garage rock albums and also hosted the yearly Goner Fest in Memphis. Additionally, Memphis has contributed to many rap and hip-hop styles including Memphis rap, horrorcore, buck, crunk, trap, and phonk.

Several notable opera singers are from Memphis, including Ruth Welting and Kallen Esperian. The New York Metropolitan Opera began coming to Memphis in 1906, their first road show, but in the 1990s decided to only visit larger cities.

Memphis is the subject of many major pop and country songs, including "The Memphis Blues" by W. C. Handy, "Memphis" by Chuck Berry, "Queen of Memphis" by Confederate Railroad, "Memphis Soul Stew" by King Curtis, "Maybe It Was Memphis" by Pam Tillis, "Graceland" by Paul Simon, "Memphis Train" by Rufus Thomas, "All the Way from Memphis" by Mott the Hoople, "Wrong Side of Memphis" by Trisha Yearwood, "Walking in Memphis" by Marc Cohn, "Stuck Inside of Mobile with the Memphis Blues Again" by Bob Dylan, and "Memphis Skyline" by Rufus Wainwright.

In addition, Memphis is mentioned in scores of other songs, including "Proud Mary" by Creedence Clearwater Revival, "Honky Tonk Women" by the Rolling Stones, "Life Is a Highway" by Tom Cochrane, "Black Velvet" by Alannah Myles, "Cities" by Talking Heads, "Crazed Country Rebel" by Hank Williams III, "Pride (In The Name Of Love)" by U2, and many others.