The work was mentioned in 1648 by writer and painter Carlo Ridolfi as a large panel commissioned in memory of Venetian politician and diplomat Pietro Cappello; he described it as "one of the most beautiful and delicate by the artist".

[7] Pietro Capello is interred in the Church of San Zaccaria and above his tomb was adorned with a painting made around 1500 that was created in the workshop of Giovanni Bellini, but it showed the Presentation in the Temple (titled the Circumcision and now in the National Gallery of Art, London), not the Virgin and Child enthroned.

[7] The work is set in a large niche, depicting a sacred conversation within an established scheme: the Madonna and Child enthroned, a musician angel on a step and four saints placed symmetrically at the sides.

[9] Tempera is an egg based painting substance that dries quickly making it easy to use and layer over, a popular choice among artists during the period.

[13] The altarpiece is set in a large semi-circular niche, known as an apse, and depicts in a pyramidal (triangular) composition of the Virgin and Child enthroned, surrounded by four saints and an angel.

[15][14] Most of these devotional paintings, while exhibiting variations in their iconographic details, show a deep influence of Byzantine art and stylistic principles.

[15][17][10] This feature may have been inspired by the now-lost work of Alvise Vivarini, an altarpiece made for Santa Maria dei Battuti, Belluno (formerly Kaiser-Friedrich Museum, Berlin, destroyed in 1945).

[18][19] Virgin Mary and Christ-child are at the top of the pyramid scheme of the altarpiece, making them the main focus as a result of linear perspective.

[11][20] Finally, in the center, an angel sits on the bottom step of the marble throne playing the lira de braccio, a violin-like instrument.

[20] The music-making angel is pictured with its lira de braccio to allow the audience to imagine its peaceful tune in the tranquil environment and to offer comfort.

[21] The angel wears a combination of cool green and warm pinks, colors and tones that are observed throughout the painting: in the mosaic above, the nearby landscape, and the surrounding architecture.

[12] The sacra conversazione (sacred conversation), which was originally developed in Florence and the popularized in Venice, is a genre of religious devotional works that shows the Virgin Mary with the Christ child upon a throne, surrounded by saints and angels which united them all into one space of harmony.

[11][22][23] The sacra conversazione is marked by the bright, vibrant colors in the San Zaccaria altarpiece, and was painted with an intent to create a beautiful space of worship.

[11] Moreover, the figures of the altarpiece are shown in a calm, meditative state; all motion has stopped, calling the viewer to pause for prayer or reflection.

[14] The mask is framed with a crown and a halo-like appearance of pomegranate leaves printed on a woven brocade cloth, as an honorary tribute to God.

[10] Ostrich eggs were typically hung over altars that were dedicated to the Virgin Mary and can be found in earlier Italian Renaissance paintings, including Andrea Mantegna's San Zeno Altarpiece (c. 1456–1459) and Pierro della Francesca's Brera Madonna (1472).

[15] Moreover, the San Zaccaria Altarpiece is acknowledged as Bellini's prime example of his life-long exploration into the effects of light and color and impressive realism that is set against classically-inspired architectural components, reflecting a culmination of his style.

[20] The depth of the artwork created by linear perspective and the carved pillars surrounding the altarpiece make the frame appear as an entrance into the image itself.

[25] Bellini made sure to add ornamental delicacy, vibrant colors, and luxurious materials as a tribute to the church's architect, Mauro Codussi.