The work can be seen as an example of Sacra conversazione (Holy Conversation), where Mary is sitting on a tall marble throne, and she's holding the Child. At Mary's feet, there are 3 musician angels, while at her side, there are 6 saints, in symmetrical positions. On the left, there's Saints Francis, John the Baptist plus Job. Saints Dominic, Louis of Toulouse and Sebastian are seen on the right. The child's features are the same as the ones in the Contarini Madonna, which is housed in the art museum called Accademia Gallery in Florence.
The upper part of the painting features a perspective coffered ceiling, which is flanked with pillars that are copies of the original ones at the altar which was the original. There is a dark niche behind the Madonna. A gilt mosaic decoration, made in the Venetian style, is in the latter's half-dome. By including Byzantine architectural and traditional Venetian elements in the altarpiece scenery, he managed to please his patrons. He did this by including established practices while at the same time introducing new artistic components to the society.
San Giobbe Altarpiece is among the masterworks of Giovanni's mature period, and it was painted for the 2nd left altar of the 15th-century Roman Catholic church, Church of St Job in Venice. The altarpiece was most likely inspired by Antonello da Messina's San Cassiano Altarpiece, then he absorbed and further developed this work's innovations. However, the dating of the painting by Giovanni is not certain, such dependency can't be proved. This is one of Bellini's most famous works, a claim that was made as earlier during De Urbe Sito, which is a description of Venice that Marco Antonio Sabellico made (1487 to 1491).
Saints Sebastian and Job depiction indicates that the picture was might be produced in connection with the 1487 plague. The dating of this work is disputed and ranges between the early 1470s and the late 1480s. In 1581, Jacopo Sansovino wrote that the work for this altarpiece was the first time Bellini used oil painting, implying an earlier date, closer to the altarpiece by Antonello. Yet, most scholars have disputed this claim. San Giobbe Altarpiece stayed in the Church of St Job until 1814 to 1818.