The band was originally called "Eric Clapton and Friends". The name "Derek and the Dominos" was a fluke that occurred when the band's provisional name of "Del and the Dynamos" was misread as Derek and the Dominos. Clapton's biography states that Tony Ashton of Ashton, Gardner and Dyke told Clapton to call the band "Del and the Dominos", since "Del" was his nickname for Eric Clapton. Del and Eric were combined and the final name became "Derek and the Dominos".
Clapton's close friendship with George Harrison brought him into contact with Harrison's wife, Pattie Boyd, with whom he became deeply infatuated. When she spurned his advances, Clapton's unrequited affections prompted most of the material for the Dominos' album, Layla and Other Assorted Love Songs (1970). Heavily blues-influenced, the album features the twin lead guitars of Clapton and Duane Allman, with Allman's slide guitar as a key ingredient of the sound. Working at Criteria Studios in Miami with Atlantic Records producer Tom Dowd, who had worked with Clapton on Cream's Disraeli Gears, the band recorded a double album.
The album features the hit love song "Layla", inspired by the classical poet of Persian literature, Nizami Ganjavi's The Story of Layla and Majnun, a copy of which Ian Dallas had given to Clapton. The book moved Clapton profoundly, as it was the tale of a young man who fell hopelessly in love with a beautiful, unavailable woman and who went crazy because he could not marry her. The two parts of "Layla" were recorded in separate sessions: the opening guitar section was recorded first, and for the second section, laid down a few weeks later, drummer Jim Gordon played the piano part for the melody which he claimed to have written (though Bobby Whitlock stated that Rita Coolidge wrote it).
The Layla LP was actually recorded by a five-piece version of the group, thanks to the unforeseen inclusion of guitarist Duane Allman of the Allman Brothers Band. A few days into the Layla sessions, Dowd—who was also producing the Allmans—invited Clapton to an Allman Brothers outdoor concert in Miami. The two guitarists met first on stage, then played all night in the studio, and became friends. Duane first added his slide guitar to "Tell the Truth" and "Nobody Knows You When You're Down and Out". In four days, the five-piece Dominos recorded "Key to the Highway", "Have You Ever Loved a Woman" (a blues standard popularised by Freddie King and others), and "Why Does Love Got to be So Sad". In September, Duane briefly left the sessions for gigs with his own band, and the four-piece Dominos recorded "I Looked Away", "Bell Bottom Blues", and "Keep on Growing". Duane returned to record "I am Yours", "Anyday", and "It's Too Late". On 9 September, they recorded Hendrix's "Little Wing" and the title track. The following day, the final track, "It's Too Late", was recorded.