Formed by country rock pioneer Gram Parsons, while a theology student at Harvard University, and John Nuese, a guitar player for local rock group The Trolls, who convinced Parsons to pursue a country-rock style. Parsons dropped out of Harvard before his first semester was over and immediately he and Nuese formed The International Submarine Band (ISB). The band featured Parsons on guitar and vocals, Ian Dunlop on bass and Mickey Gauvin on drums, but failed to achieve any significant success, although they are now usually considered one of the most influential pioneer country rock groups.

In early 1966, the ISB moved to New York City, where they lived in a house purchased through Parsons' large trust-fund. While in New York, the ISB recorded two singles for Goldstar Records and an album which went unreleased and was eventually lost.

Undaunted by his failure to achieve overnight commercial success with the ISB, Parsons began to consider moving the band to Los Angeles. In November, he headed out to LA's Laurel Canyon district on a scouting trip and finally convinced the band to move later in the year.

Parsons also convinced Peter Fonda to suggest a cameo for the ISB on Roger Corman's psychedelic film, The Trip, in which Fonda was starring at the time. The ISB recorded Lazy Days for the film, but the song was eventually rejected and was replaced with music by the Electric Flag, although the ISB still appeared on screen.

Frustrated by his inability to find commercial success with the ISB, Parsons soon took to playing honky-tonks in the LA area with his friend, Bob Buchanan (co-writer of Hickory Wind) and eventually decided to focus exclusively on country music. Almost immediately after Parsons informed them of his new country focus, Dunlop and Gauvin left the ISB, forming a band called the Flying Burrito Brothers.

Only days before the ISB officially split, Lee Hazelwood, owner of LHI Records, signed Parsons and Nuese to an excusive contract as the ISB. Immediately, Parsons and Nuese began their search for musicians to complete the band. Jon Corneal, a drummer from an earlier Parsons band, answered the call, though he was making a good living playing as a session musician in Nashville.

Three session musicians were hired to augment the threesome: Joe Osborn on bass, Earl Ball on piano and Jay Dee Maness on pedal steel. The newly re-formed ISB recorded their first single in July of 1967 and in November 1967 the same group, plus newcomer Chris Ethridge on bass, entered the studio to record what would become the band's only full length release, Safe At Home.

Parsons left the ISB in February 1968 to join the Byrds.