By far the most popular of all Loyset Compère's compositions, the litany-motet Ave Maria, is preserved in fully twelve contemporary sources (one 1502 printed anthology by Petrucci and eleven manuscripts), spanning nearly seventy years and at least four countries. Commentators have often compared it to the Ave Maria ... virgo serena of Josquin Desprez in popularity. In an age of rampantly popular Marian devotion both in the official Catholic liturgical calendar and among the devoted laity, a musical setting of the "Ave Maria" prayer would be highly in demand. This particular piece, which combines beauty with simplicity, is accessible to choirs of even modest accomplishment. The text contains elements appropriate to an even wider liturgical use, with lengthy quotations from the Litany of the Saints, and a Christological refrain interwoven throughout. Its flexible, omnibus prayer appears to have stylistic affinities with Compère's Motetti missales cycles, written in the early 1470s in Milan, though the piece may not have reached its final form until a decade or two later.

Though it is customarily divided by a strong cadence and double bar into two partes, this motet—called by a famous scholar the "most un-Netherlandish cantus firmus motet imaginable"—actually comprises three divisions of text and music. The first takes as its textual and musical basis the Marian Sequence "Ave Maria, gratia plena," from the Annunciation of the Archangel Gabriel to Mary (Luke 1: 42). Compère structures this first section about the altus and tenor voices: the altus sings a virtually unornamented transposition of the sequence melody, while the tenor intones the text on the sequence's original pitch G: just on monotone pitch for the first fifteen measures. Jennifer Bloxam has noted that the chant melody in the altus incorporates a variant peculiar to the Parisian chants Compère certainly knew in his earlier life.

To this tight opening, the composer adds a lengthy excerpt from the Great Litany of the Saints, containing invocations to the Trinity, to the Virgin, to the Archangels Michael, Gabriel, and Raphael, and then to a number of Saints: Sts. Francis, Nicholas, Augustine, Anthony, Benedict, and certain local saints whose entries change depending on the provenance of the manuscript source. The musical setting of this text proceeds simplistically, often merely alternating duet textures. The tenor voice (and sometimes the altus once again) sings a chant-derived cantus firmus melody for the Litany. These invocations are often punctuated by refrains of "O Christe, audi nos" ("O Christ, hear us").

A homophonic refrain-invocation, leading to a strong cadence on the modal final G, gives way to a triple-meter setting of the text "Beata es, Maria." Once again the tenor voice carries the melody, this time a monophonic lauda (identified by Jennifer Bloxam) of Italian fourteenth-century provenance. To the end of the piece, all four voices carry the musical momentum; in the tripla section, the outer voices often counterpoise a chordal hemiola to the tenor's strong iambic rhythms. The same graceful lauda melody links Compère's Ave Maria to motets by Jacob Obrecht and Antoine Brumel incorporating the same tune. This final lauda-inspired section does not appear in the earliest surviving version of the motet, possibly indicating a later revision by the composer—perhaps as late as his return to Italy in 1494, sadly, in the retinue of an invading French army under Charles VIII.

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