Mantegna was the second son of a carpenter and was apprenticed at ten to the painter Francesco Squarcione, whose Padua workshop had a reputation across Italy^[1]. Squarcione entered him in the painters' guild within a year, an unusual achievement for so young a boy, and by seventeen Mantegna had already set up on his own. Padua at the time had a strong interest in classical antiquities, and Mantegna built archaeological accuracy into his paintings from early on, alongside a developing interest in perspective that would define his mature style^[1]. From 1443 the sculptor Donatello was working in Padua on the high altar of the church of San Antonio, and Mantegna learned from watching him how to give figures and drapery a convincing, almost carved solidity^[1]. That combination, precise perspective and sculptural weight, is visible in the Uffizi Adoration.

In 1453 Mantegna married Nicolosia Bellini, daughter of the painter Jacopo Bellini and sister of Giovanni and Gentile Bellini, two of the leading artists then working in Venice^[1]. The marriage placed Mantegna at odds with his own former teacher, since Squarcione and the Bellini family were rivals, and the two men became estranged from that point. The connection with the Bellini brothers proved artistically fruitful in both directions: Giovanni and Gentile absorbed a stronger grasp of perspective from their brother-in-law, while Mantegna's own handling of colour and light grew more sophisticated through contact with the Bellini workshop, and the three artists collaborated on commissions across the following decades^[1]. The Uffizi Adoration was painted within a decade of this marriage, while Mantegna was still working independently in the Veneto rather than as a salaried court painter.

Two years after this painting, in 1460, Mantegna was appointed court painter to the Gonzaga family, the rulers of Mantua, and from then on he rarely left the city except for occasional trips to Tuscany and Rome^[1]. The appointment changed the balance of his output: work made before 1460, including the Uffizi Adoration, had been predominantly religious, but at the Gonzaga court he increasingly produced secular and allegorical subjects to match the humanist culture Mantua cultivated, culminating in the frescoed Camera degli Sposi of 1473, with its illusionistic ceiling of figures looking down from an painted sky^[1]. Mantegna was knighted in 1484, a rare honour for a painter, and later in life took up engraving, which carried his compositions to buyers who would never see the original paintings^[1].