Pietro Perugino (US: /ˌpɛrəˈdʒiːnoʊ, -ruːˈ-/ PERR-ə-JEE-noh, -⁠oo-; Italian: [ˈpjɛːtro peruˈdʒiːno]; born Pietro Vannucci or Pietro Vanucci; c. 1446/1452 – 1523), an Italian Renaissance painter of the Umbrian school, developed some of the qualities that found classic expression in the High Renaissance. Raphael became his most famous pupil.

Pietro Vannucci was born in Città della Pieve, Umbria, the son of Cristoforo Maria Vannucci. His nickname characterizes him as from Perugia, the chief city of Umbria. Scholars continue to dispute the socioeconomic status of the Vannucci family. While certain academics maintain that Vannucci worked his way out of poverty, others argue that his family was among the wealthiest in the town. His exact date of birth is not known, but based on his age at death that was mentioned by Vasari and Giovanni Santi, it is believed that he was born between 1446 and 1452.

Pietro most likely began studying painting in local workshops in Perugia such as those of Bartolomeo Caporali or Fiorenzo di Lorenzo. The date of the first Florentine sojourn is unknown; some make it as early as 1466–1470, others push the date to 1479. According to Vasari, he was apprenticed to the workshop of Andrea del Verrocchio alongside Leonardo da Vinci, Domenico Ghirlandaio, Lorenzo di Credi, Filippino Lippi, and others. Piero della Francesca is thought to have taught him perspective form. In 1472, he must have completed his apprenticeship since he was enrolled as a master in the Confraternity of St Luke.

Perugino was one of the earliest central Italian practitioners of oil painting. Some of his early works were extensive frescoes for the convent of the Gesuati fathers at San Giusto alle Mura, destroyed during the Siege of Florence; he produced many cartoons for them also, which they executed with brilliant effect in stained glass.

Perugino returned from Florence to Perugia, where his Florentine training showed in the Adoration of the Magi for the church of Santa Maria dei Servi of Perugia (c. 1476). In about 1480, he was called to Rome by Sixtus IV to paint fresco panels for the Sistine Chapel walls. The frescoes he executed there included Moses and Zipporah (often attributed to Luca Signorelli), the Baptism of Christ, and Delivery of the Keys. Pinturicchio accompanied Perugino to Rome, and was made his partner, receiving a third of the profits. He may have done some of the Zipporah subjects. The Sistine frescoes were the major high Renaissance commissions in Rome. The altar wall was also painted with the Assumption, the Nativity, and Moses in the Bulrushes. These works were later destroyed to make space for Michelangelo's Last Judgement.

Between 1486 and 1499, Perugino mainly worked between Florence and Perugia, maintaining studios in each city. According to Vasari, in Florence in September 1493, Perugino married Chiara, daughter of architect Luca Fancelli.

In 1496, the guild of the cambio (money-changers or bankers) of Perugia asked him to decorate their audience hall, the Sala delle Udienze del Collegio del Cambio. The humanist scholar Francesco Maturanzio acted as his consultant. This extensive scheme, which may have been finished by 1500, comprised the painting of the vault, showing the seven planets and the signs of the zodiac (Perugino being responsible for the designs and his assistants most probably for the majority of the execution), and the representation on the walls of two sacred subjects: the Nativity and Transfiguration; in addition, the Eternal Father, the cardinal virtues of Justice, Prudence, Temperance, Fortitude, Cato as the emblem of wisdom, and numerous life-sized figures of classic worthies, prophets, and sibyls figured in the program. On the mid-pilaster of the hall, Perugino placed his own portrait in bust-form. It is possible that Raphael, who in boyhood, toward 1496, may have been placed by his uncles under the tuition of Perugino, bore a hand in the work of the vaulting.

Perugino was made one of the priors of Perugia in 1501. On one occasion Michelangelo told Perugino to his face that he was a bungler in art (goffo nell arte): Vannucci brought an action for defamation of character, unsuccessfully. Put on his mettle by this mortifying transaction, he produced the masterpiece of the Madonna and Saints for the Certosa of Pavia, now disassembled and scattered among museums: the only portion in the Certosa is God the Father with cherubim. An Annunciation has disappeared; three panels, The Virgin Adoring the Infant Christ, Saint Michael, and Saint Raphael with Tobias are among the treasures of the National Gallery, London. This was succeeded in 1504–1507 by the Annunziata Altarpiece for the high altar of the Basilica dell'Annunziata in Florence, in which he replaced Filippino Lippi. The work was a failure, being accused of lack of innovation. Perugino lost his students; and toward 1506 he once more and finally, abandoned Florence, going to Perugia, and thence in a year or two to Rome.