The Blues went through a major development in sound and reach when it became possible to amplify the instruments of small combos – usually drums, bass, harmonica and most importantly the electric guitar. After World War II many artists, particularly in Chicago, moved to amplified electric blues, which was a major influence on Rock & Roll and later Blues Rock musicians and through them on Hard Rock and Heavy Metal music. Since then it has enjoyed a number of revivals, most recently in the 2000s, when it was picked up by bands of the Garage Rock Revival.

The electric amplification had impacts on several levels: when blues had become more and more popular throughout the 1920 and 1940s, the piano (and brass sections) had tended to dominate local club scenes – simply because it was louder than other leading instruments (such as the acoustic guitar). When amplification became possible in the late 1930s, it gave more room to the guitar, the bass and also the harmonica, enabling small blues combos to play noisier venues. As opposed to the jazzy, horn-driven sound of Jump Blues, this development established blues – and especially the guitar – as the main root for the numerous Rock genres mentioned above. Although the amplified harp played an essential role especially in the early electric blues bands, it is the sound of the guitar that is the focus of the genre, anticipating the archetype of the "guitar hero" in rock music, for example blues guitarists B.B. King and Eric Clapton.

Electric blues had become a viable economical force by the late 1940s, with hit singles among urban audiences. A key record was T-Bone Walker's "Call It Stormy Monday (But Tuesday Is Just as Bad)". As one of the earliest and most influential artists of electric blues, Walker played a highly sophisticated guitar with articulated solos. As opposed to the Delta Blues-based Chicago blues, this brand of Electric Texas Blues (sometimes called "west coast blues") draws its distinct sound from jump-blues, crooning and jazzy arrangements.

Another breakthrough was Muddy Waters' smash hit single "I Can’t Be Satisfied": Waters, who like many of his peers started out as a traditional acoustic delta blues singer, played a heavily amplified version of his acoustic Country Blues but largely left its sound intact. This spawned the probably most important and enduring branch of electric blues: Chicago Blues (sometimes called electric Chicago blues to differentiate it from Acoustic Chicago Blues), often seen as the prototype of the genre. Chess Records signed and published many of the most important electric blues performers through the 1950s and 1960s.