The American sheet music publishing industry produced a great deal of ragtime music. By 1912, the sheet music industry published three popular blues-like compositions, precipitating the Tin Pan Alley adoption of blues elements: "Baby Seals' Blues" by "Baby" F. Seals (arranged by Artie Matthews), "Dallas Blues" by Hart Wand and "Memphis Blues" by W. C. Handy.

Handy was a formally trained musician, composer and arranger who helped to popularize the blues by transcribing and orchestrating blues in an almost symphonic style, with bands and singers. He became a popular and prolific composer, and billed himself as the "Father of the Blues"; however, his compositions can be described as a fusion of blues with ragtime and jazz, a merger facilitated using the Cuban habanera rhythm that had long been a part of ragtime; Handy's signature work was the "St. Louis Blues".

In the 1920s, the blues became a major element of African American and American popular music, reaching white audiences via Handy's arrangements and the classic female blues performers. The blues evolved from informal performances in bars to entertainment in theaters. Blues performances were organized by the Theater Owners Bookers Association in nightclubs such as the Cotton Club, and juke joints, such as the bars along Beale Street in Memphis. This evolution led to a notable diversification of the styles and to a clearer division between blues and jazz. Several record companies, such as the American Record Corporation, Okeh Records, and Paramount Records, began to record African American music.

As the recording industry grew, country blues performers like Bo Carter, Blind Lemon Jefferson, Lonnie Johnson, Tampa Red and Blind Blake became more popular in the African American community. Sylvester Weaver was the first to record the slide guitar style, in which a guitar is fretted with a knife blade or the sawed-off neck of a bottle. The slide guitar became an important part of the Delta blues. The first blues recordings from the 1920s were in two categories: a traditional, rural country blues and more polished 'city' or urban blues.

Country blues performers often improvised, either without accompaniment or with only a banjo or guitar. There were many regional styles of country blues in the early 20th century. The (Mississippi) Delta blues was a rootsy sparse style with passionate vocals accompanied by slide guitar. Robert Johnson, who was little-recorded, combined elements of both urban and rural blues. Along with Robert Johnson, influential performers of this style were his predecessors Charley Patton and Son House. Singers such as Blind Willie McTell and Blind Boy Fuller performed in the southeastern "delicate and lyrical" Piedmont blues tradition, which used an elaborate fingerpicking guitar technique. Georgia also had an early slide tradition.

The lively Memphis blues style, which developed in the 1920s and 1930s around Memphis, Tennessee, was influenced by jug bands, such as the Memphis Jug Band or the Gus Cannon's Jug Stompers. Performers such as Frank Stokes, Blind Old Tom Anderson, Sleepy John Estes, Robert Wilkins, Big Boy Brazier, Joe McCoy and Memphis Minnie used a variety of unusual instruments such as washboard, fiddle, kazoo or mandolin. Memphis Minnie was famous for her virtuoso guitar style. Pianist Memphis Slim began his career in Memphis, but his quite distinct style was smoother and contained some swing elements. Many blues musicians based in Memphis moved to Chicago in the late 1930s or early 1940s and became part of the urban blues movement which blended country music and electric blues.

City or urban blues styles were more codified and elaborate. Classic female urban or vaudeville blues singers were popular in the 1920s, among them Mamie Smith, Gertrude "Ma" Rainey, Bessie Smith, and Victoria Spivey. Mamie Smith, more a vaudeville performer than a blues artist, was the first African- American to record a blues in 1920; her "Crazy Blues" sold 75,000 copies in its first month.

Ma Rainey, called the "Mother of Blues", and Bessie Smith sang "... each song around centre tones, perhaps in order to project her voice more easily to the back of a room." Smith would "...sing a song in an unusual key, and her artistry in bending and stretching notes with her beautiful, powerful contralto to accommodate her own interpretation was unsurpassed". Urban male performers included popular black musicians of the era, such Tampa Red, Big Bill Broonzy and Leroy Carr. Before WWII, Tampa Red was sometimes referred to as "The Guitar Wizard." Carr made the then-unusual choice of accompanying himself on the piano.

Boogie-woogie was another important style of 1930s and early 1940s urban blues. While the style is often associated with solo piano, boogie-woogie was also used to accompany singers and, as a solo part, in bands and small combos. Boogie-Woogie style was characterized by a regular bass figure, an ostinato or riff and shifts of level in the left hand, elaborating each chord and trills and decorations in the right hand. Boogie-woogie was pioneered by the Chicago-based Jimmy Yancey and the Boogie-Woogie Trio (Albert Ammons, Pete Johnson and Meade Lux Lewis). Chicago boogie-woogie performers included Clarence "Pine Top" Smith and Earl Hines, who "linked the propulsive left-hand rhythms of the ragtime pianists with melodic figures similar to those of Armstrong's trumpet in the right hand".

In the 1940s, the jump blues style developed. Jump blues is influenced by big band music and uses saxophone or other brass instruments and the guitar in the rhythm section to create a jazzy, up-tempo sound with declamatory vocals. Jump blues tunes by Louis Jordan and Big Joe Turner, based in Kansas City, Missouri, influenced the development of later styles such as rock and roll and rhythm and blues. The smooth Louisiana style of Professor Longhair and, more recently, Dr. John blends classic rhythm and blues with blues styles.