Guido di Pietro was born in Vicchio al Mugello, in the countryside north of Florence in or before the year 1400. He was an established artist by 1417, when he appears in a document as a lay painter.

He joined the Dominican order sometime between 1419 and 1422, residing at the priory of San Domenico at Fiesole.  From that time forward, he was known as Fra Giovanni.

Angelico remained in the Fiesole priory until 1439,
when he was [called] to San Marco, in Florence. 

He received commissions for important altarpieces from his own monastery, San Domenico, in Fiesole, from other Dominican houses in Florence, Cortona, and Perugia, and from religious institutions as far away as Brescia in the north of Italy and Orvieto and Rome to the south.

His prominence as an artist was challenged in Florence only by the brief and meteoric career of Masaccio (1401–1428), many of whose innovations Angelico anticipated in his own, still little-understood early works. By the time Masaccio left Florence for Rome in 1427, Angelico was indisputably the leading painter in Tuscany, a position he maintained for nearly thirty years, eclipsing the reputations of such gifted artists as Fra Filippo Lippi (1406–1469), Domenico Veneziano (ca. 1410–1461), and even the young Piero della Francesca (ca. 1406/12–1492).

Fra Giovanni was first called "pictor angelicus," the Angelic Painter, shortly after his death in 1455, a name that came to be rendered in English as Fra Angelico.

In 1984, Fra Angelico was beatified—the first step in the process toward sainthood—by Pope John Paul II. The latter declared him the patron of artists two years later.