Although usually named together as the three giants of the High Renaissance, Leonardo, Michelangelo and Raphael were not of the same generation. Leonardo was 23 when Michelangelo was born and 31 when Raphael was born. Raphael died at the age of 37 in 1520, the year after Leonardo died, but Michelangelo went on creating for another 45 years.

Leonardo was born on 14/15 April 1452 in the Tuscan hill town of Vinci, in the lower valley of the Arno river in the territory of the Medici-ruled Republic of Florence.

Leonardo spent his first years in the hamlet of Anchiano in the home of his mother, and from at least 1457 lived in the household of his father, grandparents and uncle in the small town of Vinci.

His father had married a 16-year-old girl named Albiera Amadori, who loved Leonardo but died young in 1465 without children.

In the mid-1460s, Leonardo's family moved to Florence, and around the age of 14, he became a garzone (studio boy) in the workshop of Verrocchio, who was the leading Florentine painter and sculptor of his time.

Florence at the time of Leonardo's youth was the centre of Christian Humanist thought and culture. Leonardo commenced his apprenticeship with Verrocchio in 1466, the year that Verrocchio's master, the great sculptor Donatello, died.

In 1468, when Leonardo was 16, his father married again to 20-year-old Francesca Lanfredini, who also died without children.

Leonardo became an apprentice by the age of 17 and remained in training for seven years.

Piero's legitimate heirs were born from his third wife Margherita di Guglielmo, who gave birth to six children, and his fourth and final wife, Lucrezia Cortigiani, who bore him another six heirs. In all, Leonardo had 12 half-siblings, who were much younger than he was (the last was born when Leonardo was 40 years old) and with whom he had very little contact.

By 1472, at the age of 20, Leonardo qualified as a master in the Guild of Saint Luke, the guild of artists and doctors of medicine, but even after his father set him up in his own workshop, his attachment to Verrocchio was such that he continued to collaborate and live with him.

Leonardo's earliest known dated work is a 1473 pen-and-ink drawing of the Arno valley, which has been cited as the first "pure" landscape in the Occident. According to Vasari, the young Leonardo was the first to suggest making the Arno river a navigable channel between Florence and Pisa.

In 1476, during the time of Leonardo's association with Verrocchio's workshop, the Portinari Altarpiece by Hugo van der Goes arrived in Florence, bringing from Northern Europe new painterly techniques that were to profoundly affect Leonardo, Ghirlandaio, Perugino and others.

In January 1478, Leonardo received an independent commission to paint an altarpiece for the Chapel of St. Bernard in the Palazzo Vecchio, an indication of his independence from Verrocchio's studio.

Leonardo's political contemporaries were Lorenzo de' Medici (il Magnifico), who was three years older, and his younger brother Giuliano, who was slain in the Pazzi conspiracy in 1478. Leonardo was sent as an ambassador by the Medici court to Ludovico il Moro, who ruled Milan between 1479 and 1499.

Leonardo was a contemporary of Botticelli, Domenico Ghirlandaio and Perugino, who were all slightly older than he was. He would have met them at the workshop of Verrocchio, with whom they had associations, and at the Academy of the Medici. Botticelli was a particular favourite of the Medici family, and thus his success as a painter was assured. Ghirlandaio and Perugino were both prolific and ran large workshops. They competently delivered commissions to well-satisfied patrons who appreciated Ghirlandaio's ability to portray the wealthy citizens of Florence within large religious frescoes, and Perugino's ability to deliver a multitude of saints and angels of unfailing sweetness and innocence. These three were among those commissioned to paint the walls of the Sistine Chapel, the work commencing with Perugino's employment in 1479.

One anonymous writer (Anonimo Gaddiano or Anonimo Fiorentino ("the anonymous Florentine")) claims that in 1480, Leonardo was living with the Medici and often worked in the garden of the Piazza San Marco, Florence, where a Neoplatonic academy of artists, poets and philosophers organized by the Medici met.

In March 1481, Leonardo received a commission from the monks of San Donato in Scopeto for The Adoration of the Magi. Neither of these initial commissions were completed, being abandoned when Leonardo went to offer his services to Duke of Milan Ludovico Sforza.

In 1482, Leonardo casted a silver stringed instrument from a horse's skull and ram horns to bring to Sforza (Duke of Milan Ludovico Sforza), whom he wrote a letter describing the diverse things that he could achieve in the fields of engineering and weapon design, and mentioning that he could paint.

Leonardo worked in Milan from 1482 until 1499. He was commissioned to paint the Virgin of the Rocks for the Confraternity of the Immaculate Conception and The Last Supper for the monastery of Santa Maria delle Grazie.

In a letter of 1482 to the lord of Milan Ludovico il Moro (Ludovico Sforza), Leonardo wrote that he could create all sorts of machines both for the protection of a city and for siege. When he fled from Milan to Venice in 1499, he found employment as an engineer and devised a system of moveable barricades to protect the city from attack.

In the spring of 1485, Leonardo travelled to Hungary on behalf of Sforza (Duke of Milan) to meet king Matthias Corvinus, and was commissioned by him to paint a Madonna.

Leonardo's most famous painting of the 1490s is The Last Supper, commissioned for the refectory of the Convent of Santa Maria della Grazie in Milan. It represents the last meal shared by Jesus with his disciples before his capture and death, and shows the moment when Jesus has just said "one of you will betray me", and the consternation that this statement caused.

It is recorded that in 1492, Leonardo, with assistants painted the Sala delle Asse in the Sforza Castle in Milan, with a trompe-l'œil depicting trees, with an intricate labyrinth of leaves and knots on the ceiling.

Leonardo's approach to science was observational: he tried to understand a phenomenon by describing and depicting it in utmost detail and did not emphasise experiments or theoretical explanation. Since he lacked formal education in Latin and mathematics, contemporary scholars mostly ignored Leonardo the scientist, although he did teach himself Latin. In the 1490s he studied mathematics under Luca Pacioli and prepared a series of drawings of regular solids in a skeletal form to be engraved as plates for Pacioli's book Divina proportione, published in 1509. While living in Milan, he studied light from the summit of Monte Rosa.

Leonardo was employed on many other projects for Sforza, including the preparation of floats and pageants for special occasions, a drawing and wooden model for a competition to design the cupola for Milan Cathedral (which he withdrew), and a model for a huge equestrian monument to Ludovico's predecessor Francesco Sforza. This would have surpassed in size the only two large equestrian statues of the Renaissance, Donatello's Gattamelata in Padua and Verrocchio's Bartolomeo Colleoni in Venice, and became known as the Gran Cavallo. Leonardo completed a model for the horse and made detailed plans for its casting, but in November 1494, Ludovico gave the bronze to his brother-in-law (Ercole I d'Este, Duke of Ferrara) to be used for a cannon to defend the city from Charles VIII.

With Ludovico Sforza overthrown at the dawn of the Second Italian War, Leonardo, with his assistant Salaì and friend, the mathematician Luca Pacioli, fled Milan for Venice. There, he was employed as a military architect and engineer, devising methods to defend the city from naval attack.

On his return to Florence in 1500, Leonardo and his household were guests of the Servite monks at the monastery of Santissima Annunziata and were provided with a workshop where, according to Vasari, Leonardo created the cartoon of The Virgin and Child with St Anne and St John the Baptist, a work that won such admiration that "men and women, young and old" flocked to see it "as if they were attending a great festival."

In Cesena in 1502, Leonardo entered the service of Cesare Borgia, the son of Pope Alexander VI, acting as a military architect and engineer and travelling throughout Italy with his patron.

By this same month, Leonardo had begun working on a portrait of Lisa del Giocondo, the model for the Mona Lisa, which he would continue working on until his twilight years.

A prevalent tradition in Florence was the small altarpiece of the Virgin and Child. Many of these were created in tempera or glazed terracotta by the workshops of Filippo Lippi, Verrocchio and the prolific della Robbia family. Leonardo's early Madonnas such as The Madonna with a carnation and the Benois Madonna followed this tradition while showing idiosyncratic departures, particularly in the latter in which the Virgin is set at an oblique angle to the picture space with the Christ Child at the opposite angle. This compositional theme was to emerge in Leonardo's later paintings such as The Virgin and Child with St. Anne.

Leonardo had left Borgia's service and returned to Florence by early 1503, where he rejoined the Guild of Saint Luke on 18 October of that year.

In January 1504, Leonardo was part of a committee formed to recommend where Michelangelo's statue of David should be placed.

In 1507, Leonardo was in Florence sorting out a dispute with his brothers over the estate of his father, who had died in 1504.

Leonardo then spent two years in Florence designing and painting a mural of The Battle of Anghiari for the Signoria, with Michelangelo designing its companion piece, The Battle of Cascina.

In 1506, Leonardo was summoned to Milan by Charles II d'Amboise, the acting French governor of the city. The Council of Florence wished Leonardo to return promptly to finish The Battle of Anghiari, but he was given leave at the behest of Louis XII, who considered commissioning the artist to make some portraits.

By 1508, Leonardo was back in Milan, living in his own house in Porta Orientale in the parish of Santa Babila.

Leonardo started his study in the anatomy of the human body under the apprenticeship of Andrea del Verrocchio, who demanded that his students develop a deep knowledge of the subject. As an artist, he quickly became master of topographic anatomy, drawing many studies of muscles, tendons and other visible anatomical features. As a successful artist, Leonardo was given permission to dissect human corpses at the Hospital of Santa Maria Nuova in Florence and later at hospitals in Milan and Rome. From 1510 to 1511 he collaborated in his studies with the doctor Marcantonio della Torre. Leonardo made over 240 detailed drawings and wrote about 13,000 words towards a treatise on anatomy. Only a small amount of the material on anatomy was published in Leonardo's Treatise on painting.

In 1512, Leonardo was working on plans for an equestrian monument for Gian Giacomo Trivulzio, but this was prevented by an invasion of a confederation of Swiss, Spanish and Venetian forces, which drove the French from Milan. Leonardo stayed in the city, spending several months in 1513 at the Medici's Vaprio d'Adda villa.

From September 1513 to 1516, Leonardo spent much of his time living in the Belvedere Courtyard in the Apostolic Palace, where Michelangelo and Raphael were both active.

In March of that year, Lorenzo de' Medici's son Giovanni assumed the papacy (as Leo X); Leonardo went to Rome that September, where he was received by the pope's brother Giuliano.

In October 1515, King Francis I of France recaptured Milan.

Leonardo was present at the 19 December meeting of Francis I and Leo X, which took place in Bologna.

In 1516, Leonardo entered Francis' service, being given the use of the manor house Clos Lucé, near the king's residence at the royal Château d'Amboise. Being frequently visited by Francis, he drew plans for an immense castle town the king intended to erect at Romorantin, and made a mechanical lion, which during a pageant walked toward the king and—upon being struck by a wand—opened its chest to reveal a cluster of lilies. Leonardo was accompanied during this time by his friend and apprentice, Francesco Melzi, and supported by a pension totalling 10,000 scudi. At some point, Melzi drew a portrait of Leonardo; the only others known from his lifetime were a sketch by an unknown assistant on the back of one of Leonardo's studies (c. 1517) and a drawing by Giovanni Ambrogio Figino depicting an elderly Leonardo with his right arm assuaged by cloth. The latter, in addition to the record of an October 1517 visit by Louis d'Aragon, confirms an account of Leonardo's right hand being paralytic at the age of 65, which may indicate why he left works such as the Mona Lisa unfinished. He continued to work at some capacity until eventually becoming ill and bedridden for several months.

Leonardo died at Clos Lucé on 2 May 1519 at the age of 67, possibly of a stroke.

On 12 August 1519, Leonardo's remains were interred in the Collegiate Church of Saint Florentin at the Château d'Amboise.

Leonardo's youth was spent in a Florence that was ornamented by the works of these artists and by Donatello's contemporaries, Masaccio, whose figurative frescoes were imbued with realism and emotion; and Ghiberti, whose Gates of Paradise, gleaming with gold leaf, displayed the art of combining complex figure compositions with detailed architectural backgrounds. Piero della Francesca had made a detailed study of perspective, and was the first painter to make a scientific study of light. These studies and Alberti's treatise De pictura were to have a profound effect on younger artists and in particular on Leonardo's own observations and artworks.

Salvator Mundi, a painting by Leonardo depicting Jesus holding an orb, sold for a world record US$450.3 million at a Christie's auction in New York, 15 November 2017.

On the 500th anniversary of Leonardo's death, the Louvre in Paris arranged for the largest ever single exhibit of his work, called Leonardo, between November 2019 and February 2020. The exhibit includes over 100 paintings, drawings and notebooks. Eleven of the paintings that Leonardo completed in his lifetime were included. Five of these are owned by the Louvre, but the Mona Lisa was not included because it is in such great demand among general visitors to the Louvre; it remains on display in its gallery. Vitruvian Man, however, is on display following a legal battle with its owner, the Gallerie dell'Accademia in Venice. Salvator Mundi was also not included because its Saudi owner did not agree to lease the work.