Written between 1954 and 1957, the poem is the product of Kerouac's spontaneous prose technique, his Buddhist faith, emotional states, and disappointment with his own creativity—including his failure to publish a novel between 1950's The Town and the City and the more widely acclaimed On the Road (1957).

Rexroth mainly criticized Kerouac's perceived misunderstanding of Buddhism, referring to his portrayal of Buddha as "a dime-store incense burner", and sardonically concluded that he "always wondered what ever happened to those wax work figures in the old rubber-neck dives in Chinatown.

"[7] Ginsberg, in observations recorded in Barry Gifford and Lawrence Lee's oral history Jack's Book (1978), attributed Rexroth's "damning, terrible" review and his condemnation of the Beat phenomenon to Rexroth feeling vulnerable as a result of the perception that "he had now 'shown his true colors' by backing a group of unholy, barbarian, no-account, no-good people – Beatnik, unwashed, dirty, badmen of letters who didn't have anything on the ball.

[9] Creeley himself had published a more positive review in Poetry,[9] which described the poem as "a series of improvisations, notes, a shorthand of perceptions and memories, having in large part the same word-play and rhythmic invention to be found in [Kerouac's] prose.

But what seems to me to emerge at the end is a voice of remarkable kindness and gentleness, an engaging and modest good humor and a quite genuine spiritual simplicity...[14]Jones has described Mexico City Blues as definitive documentation of Kerouac's attempt to achieve both psychic and literary equilibrium.

In this sense, Mexico City Blues is the most important book Kerouac ever wrote, and it sheds light on all his novels by providing a compendium of the issues that most concerned him as a writer, as well as a model for the transformation of conflict into an antiphonal language.