Histoire de Melody Nelson is considered by many critics and fans to be Gainsbourg's most influential and accomplished work, as well as one of the greatest French-language albums in popular music history.

[3] At just under twenty-eight minutes, the short running time and the stylistic consistency and similarity throughout Histoire de Melody Nelson give it qualities more in line with an extended play or a single continuous suite.

It depicts Gainsbourg's partner Jane Birkin wearing a red wig, and with her jeans rolled down slightly to accommodate her early stage of pregnancy.

"[8] Tom Ewing of Pitchfork gave the album a perfect score, particularly praising the opening and closing tracks as depictions of "the black spaces of a man's interior."

Edwards of PopMatters commented that "anyone with an interest in hearing a blueprint for trip hop or a master class in the depiction of desire in pop music, should be sure to listen to this mysterious, timeless, contradictory album.

"[10] Histoire de Melody Nelson is regarded by many critics and fans to be Gainsbourg's magnum opus and his most influential release.

While it became a pivotal album of the 1970s and was instrumental in the development of French rock and the trip hop movement of the 1990s, it has also influenced many musical artists outside France, including Jarvis Cocker of Pulp, Beck, Tricky, Broadcast, Barry Adamson of Magazine, David Holmes, Cibo Matto, Neil Hannon of the Divine Comedy, Stereolab, Michael Stipe of R.E.M., Portishead, The Last Shadow Puppets and Arctic Monkeys.

[9][13][14] Faith No More and Mr. Bungle vocalist Mike Patton has also expressed his appreciation for the album and Gainsbourg's music, stating that he "was immediately awe-struck by the elegance, variety and detail of Serge's 'pop' forms...it made [me] think that [I] had a lot to learn".

He also joined the stage with frequent collaborator PJ Harvey in 1996 for performances of two Gainsbourg songs, "Bonnie and Clyde" and "Harley Davidson".

The BBC Concert Orchestra, the Crouch End Festival Chorus and a children’s string quintet were also part of the show.

On 22 and 23 October 2008, Jean-Claude Vannier performed the album live at the Cité de la Musique with guest vocalists Mathieu Amalric, Brigitte Fontaine, Brian Molko, Martina Topley-Bird, Daniel Darc, Clotilde Hesme, and Seaming To.

Each of the album's songs were performed by different combinations of the evening's artists, backed by the Hollywood Bowl Orchestra and the Cal State Fullerton chorale.