According to tradition, Agnello of Naples, now co-patron (compatrono) of the city of Naples, is buried in the Sant'Agnello Maggiore. Agnello was a 6th-century Neapolitan bishop, who defended the city against the besieging Lombards. Supposedly the church had been founded and devoted to the Virgin, by Agnello's parents. Recent studies have shown that the church was built atop an Ancient Roman Acropolis from the 4th century. When Sant'Agnello died, the church's name was changed to Santa Maria dei Sette Cieli (of the Seven Heavens). In the 9th century, Bishop Athanasius of Naples built a new religious building and dedicated to the abbot Saint Agnello and placed his relics in the church. During the Middle Ages, the cult of Sant'Agnello became increasingly important and the end of the 13th century till 1517.
From 1510 to 1600, the church rebuilt and enlarged by the archbishop Giovanni Maria Poderico. The transept, previously the church of Santa Maria Intercede was reconstructed as part of this church in 1517 and work inside continued on till the 18th century. The main altar by Girolamo Santacroce, had additions by Giovanni Battista Pandullo. Vincenzo Martinoredid the pavement.
On August 7, 1809, the monastic order in charge of the church was suppressed and sold by the Minister of Finance to a private citizen Cosimo d'Orazio. The second world war added damage. In 1962, during reconstruction the remains of the ancient acropolis were found. Vandalism, earthquakes, and decay have contributed to its poor state of conservation. In 2011, after a long restoration, the church has reopened.
The church still retains medieval traces in bas reliefs. The paintings moved here are of uncertain attribution. Only the main altar sculpted by Girolamo Santacroce is original.
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