New Orleans rhythm and blues is a style of rhythm and blues that originated in New Orleans. It was a direct precursor to rock and roll and strongly influenced ska. Instrumentation typically includes drums, bass, piano, horns, electric guitar, and vocals. The style is characterized by syncopated "second line" rhythms, a strong backbeat, and soulful vocals. Artists such as Roy Brown, Dave Bartholomew, and Fats Domino are representative of the New Orleans R&B sound.

New Orleans rhythm and blues can be characterized by predominant piano, "singing" horns, and call-and-response elements. Clear influences of Kansas City Swing bands can be heard through the extensive use of trumpet and saxophone solos. A "double" bass line, when the guitar and bass play in unison, was combined with a strong backbeat to make the music easy to dance to. It is also common to hear the influence of Caribbean rhythms such as the mambo, rhumba, and the calypso.

In addition, the usage of blue notes is characteristic. Like most blues, New Orleans R&B typically follows a standard three-stanza form that contains tonic, subdominant, and dominant chords. Within these chords, the three "blue notes", also known as flatted notes, are the third, fifth, and seventh scale degrees. In New Orleans R&B, the flatted third is particularly notable.

New Orleans rhythm and blues was pioneered by local barrelhouse pianists Champion Jack Dupree, Archibald, and Professor Longhair.

Professor Longhair, otherwise known as "Fess", was considerably influential in the development of the New Orleans R&B sound. Allen Toussaint, an important figure in New Orleans R&B, described him as "The Bach of Rock 'n' Roll". He combined Caribbean and boogie-woogie rhythms to create his signature style. The result was a usage of polyrhythms that he often whistled while playing. Although he was admired by other New Orleans musicians, he did not gain national attention until the end of his career.

During his early career, Longhair visited the Caldonia Inn to listen to Dave Bartholomew's band. When he sat in for Bartholomew's pianist, a large crowd suddenly flooded the venue. He then decided to start his own band called the Four Hairs combo. Soon after, the band recorded their first four tunes at the Hi-Hat club for the Star Talent Label. In 1950, Longhair worked briefly with Mercury Records and recorded "Bald Head". The song reached No.5 on Billboard's R&B chart. Due to financial complications, his work with Mercury was cut short. During the 1950s, he worked with Atlantic Records and recorded "Tipitina", which at the time was only a local hit, but today is recognized as a New Orleans R&B classic.

There were two types of local pianists in New Orleans; "professor" pianists and "barrelhouse" pianists. Professors were often classically trained and understood music theory. They played in a variety of styles in the brothels of Storyville. Because they were more skilled, audiences expected them to play any request that was thrown their way. Notable "professor" pianists include Buddy Christian, Clarence Williams, Alton Purnell, Spencer Williams, and Jelly Roll Morton. Barrelhouse pianists were often untrained with little to no background in music theory. They were mostly self-taught and played mostly in a blues style. Barrelhouse pianists were considered semi-professional and played for drinks, food, or tips.

Roy Brown, Dave Bartholomew, Paul Gayten, Smiley Lewis, Fats Domino, Annie Laurie, and Larry Darnell were the primary artists who achieved national fame.