The poem consists of three parts, with an additional footnote.
Ginsberg says that Part II, in relation to Part I, "names the monster of mental consciousness that preys on the Lamb". Part II is a rant about the state of industrial civilization, characterized in the poem as 'Moloch'. Ginsberg was inspired to write Part II during a period of peyote-induced visionary consciousness in which he saw a hotel façade as a monstrous and horrible visage which he identified with that of Moloch. Moloch is the biblical idol in Leviticus to whom the Canaanites sacrificed children. Ginsberg intends that the characters he portrays in Part I be understood to have been sacrificed to this idol. Moloch is also the name of an industrial, demon-like figure in Fritz Lang's Metropolis, a film which Ginsberg credits with influencing "Howl, Part II" in his annotations for the poem (see especially Howl: Original Draft Facsimile, Transcript & Variant Versions). Most lines in this section contain the fixed base "Moloch". Ginsberg says of Part II, "Here the long line is used as a stanza form broken into exclamatory units punctuated by a base repetition, Moloch".
The closing section of the poem is the "Footnote", characterized by its repetitive 'Holy!' mantra, an ecstatic assertion that everything is holy. It can be read as the antithesis of Part II. Ginsberg says, "I remembered the archetypal rhythm of Holy Holy Holy weeping in a bus on Kearny Street, and wrote most of it down in notebook there ... I set it as Footnote to Howl because it was an extra variation of the form of Part II".
The frequently quoted (and often parodied) opening lines set the theme and rhythm for the poem:
I saw the best minds of my generation destroyed by madness, starving hysterical naked,
dragging themselves through the negro streets at dawn looking for an angry fix;
Angel-headed hipsters burning for the ancient heavenly connection
to the starry dynamo in the machinery of night.
Ginsberg's own commentary discusses the work as an experiment with the "long line". For example, Part I of the poem is structured as a single run-on sentence with a repetitive refrain dividing it up into breaths. Ginsberg said, "Ideally each line of Howl is a single breath unit. My breath is long - that's the measure, one physical-mental inspiration of thought contained in the elastic of a breath".