Born in Florence, he was the illegitimate son of Cosimo de' Medici (the Elder) and a slave-woman named Maddalena, who was said to have been purchased in Venice.

that his mother might have been a black African, because of the apparently dusky skin depicted in Mantegna's portrait of Carlo, which however it is more likely due to aging of the pigments or other similar causes.

Carlo was portrayed by Andrea Mantegna in a head-and-shoulders portrait wearing the clerical garb of a protonotary apostolic in 1466.

He also appears in the funeral scene of Filippo Lippi's Stories of St. Stephen and St. John the Baptist in the Prato Cathedral, in which he is depicted standing behind the Pope.

[24] In the historical fantasy series Da Vinci's Demons, Carlo was played by actor Ray Fearon.