His father, Benedetto de' Franceschi, was a tanner and shoemaker. He was wealthy enough to educate his son. Piero's early training as a painter is a blank slate. However, he probably did an apprenticeship with someone.

When he was 20, Piero worked as an associate of Domenico Veneziano, then painting frescoes in Florence.

Misericordia Polyptych (detail)
Saint Sebastian
and St. John the Baptist
1445-48
panel; 108 x 45 cm (each)
Pinacoteca Comunale
San Sepolcro, Italy

Duke of Urbano
Federico da Montefeltro
1465-66
panel, 47 x 33 cm
Uffizi, Florence, Italy

The famous diptych portrait of the Urbino couple, Count Federico and his consort, Battista Sforza (Uffizi, Florence), probably commemorates their marriage in 1465.

As an old man Piero seems to have abandoned painting in favour of writing about painting and mathematics. He wrote a treatise on painting: De prospectiva pingendi "On Perspective in Painting". He dedicated it to his patron, the Duke of Urbino.

It is not known how he died.