Formed by guitarist/singer Eric Clapton with other former members of Delaney & Bonnie & Friends in the spring of 1970. The rest of the lineup was Bobby Whitlock (keyboards, vocals), Carl Radle (bass) and Jim Gordon (drums).

The group debuted at the Lyceum Ballroom in London in June 1970 and undertook a summer tour of England. From late August to early October, they recorded the celebrated double album Layla and Other Assorted Love Songs (November 1970) with guitarist Duane Allman sitting in. They then returned to touring in England and the US., playing their final date in December.

The Dominos reconvened to record a second album in May 1971, but split up without completing it.

Clapton then retired from the music business, nursing a heroin addiction. In his absence, and in the wake of Allman's death in a motorcycle accident in October 1971, the Dominos and Layla gained in stature. Re-released as a single at its full, 7-minute length, Layla charted in the US and UK in the summer of 1972. A live album, Derek and the Dominos in Concert (January 1973), taken from the 1970 US tour, was also a strong seller.

Time has only added to the renown of the group, which is now rated among Clapton's most outstanding achievements. The 1988 Clapton box set retrospective Crossroads featured material from the abortive second album sessions. The Layla Sessions was a 1990 box set expanding that album across 3 CDs. Live at the Fillmore (1994) offered an expanded version of the In Concert album.