The portrait was commissioned by the art-loving Tommaso as the right-hand wing of a triptych. She was placed opposite her husband, with a now lost central Madonna and Child. Their small size and intimacy suggests that the portraits were commissioned for private prayer; some art historians believe, given that Tommaso's cultural acumen and preoccupation with his social standing, they were partially accessible to the public. The triptych may have been intended for the Portinari Chapel, located behind the apse of the Basilica of Sant'Eustorgio, Milan, and constructed between 1462 and 1468.
Maria would have been around 14 years old at the time the portrait was commissioned, either the year of her marriage in 1470 or shortly after. Tommaso represented the Medici bank in Bruges, but after a promising early career he gave a number of risky and unsecured loans to Charles the Bold which were left unpaid and eventually led to the branch's insolvency. He died young, and when the portrait was first mentioned as part of his collection in 1501, he was no longer alive. Maria is recorded as being alive at the time; she was executor to her husband's will but her fate thereafter is uncertain. The 1501 inventory places both portraits as wings, with a central Virgin and Child panel; "a small, valuable panel painting, with an image of Our Lady in the middle and on the sides painted Tommaso and mona Maria his wife" (una tavoletta dipinta preg[i]ata cum nel mezo una immagine di Nostra Donna e delle bande si è Tommaso e mona Maria sua donna dipinti in deta tavoletta).