One of the "Three Kings of the Blues Guitar" (along with B.B. King and Freddie King), he stood 6' 4" weighed in at 260 lbs (118 kg) and was known as "The Velvet Bulldozer". He was born Albert Nelson into a humble family in Indianola, Mississippi, at a cotton plantation where he worked in his early days. One of his earlier influences in music was his own father, Will Nelson, who would often play the guitar. During his childhood he would also sing at a family gospel group at a church. He began his professional work as a musician with a group called In The Groove Boys, in Osceola, Arkansas. He also briefly played drums for Jimmy Reed's band. The electric guitar became his signature instrument, his preference being the Gibson Flying V, which he named "Lucy".

His first hit was "I'm A Lonely Man", released in 1959. However, it was not until his 1961 release "Don't Throw Your Love on Me So Strong" that he had a major hit, ranking 14th on the R&B charts. In 1966 he signed with the famous Stax record label and in 1967 released his legendary album Born Under A Bad Sign. The title track of that album (written by Booker T. Jones and William Bell) became King's most well known song and has been covered by many artists (from Cream to Homer Simpson).

King was a left-handed "upside-down/backwards" guitarist: he was left-handed but usually played right-handed guitars flipped over upside-down so the low E string was on the bottom. In later years he played a custom-made guitar that was basically left-handed, but had the strings reversed (as he was used to playing). He also used very unorthodox tunings (i.e., tuning as low as C to allow him to make sweeping string bends). A "less is more" type blues player, he was known for his expressive "bending" of notes, a technique characteristic of blues guitarists. Jimi Hendrix also played right-handed guitars that were flipped over, but in contrast, Hendrix also flipped the nut and bridge to retain the string layout (low E on top).

King influenced many later blues guitarists including Jimi Hendrix, Eric Clapton, Mick Taylor, Mike Bloomfield, Gary Moore, and especially Stevie Ray Vaughan, who also covered many of King's songs. Clapton's guitar solo on the 1968 Cream hit "Strange Brew" from the album Disraeli Gears is a close emulation of King's solo on his Stax Records hit "Oh, Pretty Woman".

One of King's last contributions was on guitarist Gary Moore's 1990 Still Got the Blues album, spawning a new version of "Oh, Pretty Woman" (a European hit single). This led to a number of guest appearances on Moore's European tours, along with Albert Collins. His last album was "Red House" released in 1991. The album featured Joe Walsh on guitar was pretty much a rock oriented effort. It featured a nice rendition of James Taylor's "Don't Let Me Be Lonely" as well as the title track, a cover of Jimi Hendrix composition.

King died on December 21, 1992 from a heart attack in Memphis, Tennessee. He has a star on the St. Louis Walk of Fame.