Antoon van Dyck (his Flemish name) was born to prosperous parents in Antwerp. His Father was Franz van Dyck, a silk merchant, and his mother was Maria, daughter of Dirk Cupers and Catharina Conincx. He was baptised on 23 March 1599 (as Anthonio). His talent was evident very early, and he was studying painting with Hendrick van Balen by 1609, and became an independent Painter around 1615, setting up a workshop with his even younger friend Jan Brueghel the Younger. By the age of fifteen he was already a highly accomplished Artist, as his Self-portrait, 1613–14, shows. He was admitted to the Antwerp painters' Guild of Saint Luke as a free master by February 1618. Within a few years he was to be the chief assistant to the dominant master of Antwerp, and the whole of Northern Europe, Peter Paul Rubens, who made much use of sub-contracted artists as well as his own large workshop. His influence on the young Artist was immense; Rubens referred to the nineteen-year-old van Dyck as "the best of my pupils".

His great success compelled van Dyck to maintain a large workshop in London, a studio which was to become "virtually a production line for portraits". According to a visitor to his studio he usually only made a drawing on paper, which was then enlarged onto canvas by an assistant; he then painted the head himself. The costume in which the client wished to be painted was left at the studio and often with the unfinished canvas sent out to artists specialised in rendering such clothing. In his last years these studio collaborations accounted for some decline in the quality of work. In addition many copies untouched by him, or virtually so, were produced by the workshop, as well as by professional copyists and later painters; the number of paintings ascribed to him had by the 19th century become huge, as with Rembrandt, Titian and others. However, most of his assistants and copyists could not approach the refinement of his manner, so compared to many masters consensus among art historians on attributions to him is usually relatively easy to reach, and museum labelling is now mostly updated (country house attributions may be more dubious in some cases). The relatively few names of his assistants that are known are Dutch or Flemish; he probably preferred to use trained Flemings, as no English equivalent training yet existed. Adriaen Hanneman (1604–71) returned to his native Hague in 1638 to become the leading portraitist there. Van Dyck's enormous influence on English art does not come from a tradition handed down through his pupils; in fact it is not possible to document a connection to his studio for any English Painter of any significance.

The origins and exact nature of their relationship are unclear; it has been speculated that van Dyck was a pupil of Rubens from about 1613, as even his early work shows little trace of van Balen's style, but there is no clear evidence for this. At the same time the dominance of Rubens in the relatively small and declining city of Antwerp probably explains why, despite his periodic returns to the city, van Dyck spent most of his career abroad. In 1620, in Rubens's contract for the major commission for the ceiling of the Carolus Borromeuskerk, the Jesuit church at Antwerp (lost to fire in 1718), van Dyck is specified as one of the "discipelen" who was to execute the paintings to Rubens' designs.

In 1620, at the instigation of George Villiers, Marquess of Buckingham, van Dyck went to England for the first time where he worked for King James I of England, receiving £100. It was in London in the collection of the Earl of Arundel that he first saw the work of Titian, whose use of colour and subtle modeling of form would prove transformational, offering a new stylistic language that would enrich the compositional lessons learned from Rubens.

After about four months, he returned to Flanders, but moved on in late 1621 to Italy, where he remained for 6 years, studying the Italian masters and beginning his career as a successful portraitist. He was already presenting himself as a figure of consequence, annoying the rather bohemian Northern artist's colony in Rome, says Giovan Pietro Bellori, by appearing with "the pomp of Zeuxis ... his behaviour was that of a nobleman rather than an ordinary person, and he shone in rich garments; since he was accustomed in the circle of Rubens to noblemen, and being naturally of elevated mind, and anxious to make himself distinguished, he therefore wore—as well as silks—a hat with feathers and brooches, gold chains across his chest, and was accompanied by servants."

Van Dyck had remained in touch with the English court and had helped King Charles's agents in their search for pictures. He had also sent back some of his own works, including a portrait (1623) of himself with Endymion Porter, one of Charles's agents, a mythological work, Rinaldo and Armida (1629, now in the Baltimore Museum of Art), and a religious picture for the Queen. He had also painted Charles's sister, Queen Elizabeth of Bohemia, at The Hague in 1632. In April of that year, van Dyck returned to London and was taken under the wing of the court immediately, being knighted in July and at the same time receiving a pension of £200 a year, in the grant of which he was described as principalle Paynter in ordinary to their majesties. He was well paid for his paintings in addition to this, at least in theory, as King Charles did not actually pay over his pension for five years, and reduced the price of many paintings. He was provided with a house on the River Thames at Blackfriars, then just outside the City, thus avoiding the monopoly of the Worshipful Company of Painter-Stainers. A suite of rooms in Eltham Palace, no longer used by the royal family, was also put at his disposal as a country retreat. His Blackfriars studio was frequently visited by the King and Queen (later a special causeway was built to ease their access), who hardly sat for another Painter while van Dyck lived.

He was mostly based in Genoa, although he also travelled extensively to other cities, and stayed for some time in Palermo in Sicily. For the Genoese aristocracy, then in a final flush of prosperity, he developed a full-length portrait style, drawing on Veronese and Titian as well as Rubens' style from his own period in Genoa, where extremely tall but graceful figures look down on the viewer with great hauteur. In 1627, he went back to Antwerp where he remained for five years, painting more affable portraits which still made his Flemish patrons look as stylish as possible. A life-size group portrait of twenty-four City Councillors of Brussels he painted for the council-chamber was destroyed in 1695. He was evidently very charming to his patrons, and, like Rubens, well able to mix in aristocratic and court circles, which added to his ability to obtain commissions. By 1630, he was described as the court Painter of the Habsburg Governor of Flanders, the Archduchess Isabella. In this period he also produced many religious works, including large altarpieces, and began his printmaking (see below).

King Charles I was the most passionate and generous collector of art among the Stuart kings, and he saw art as a way of promoting his elevated view of the monarchy. In 1628, he bought the fabulous collection that the Duke of Mantua was forced to sell, and he had been trying since his accession in 1625 to bring leading foreign Painters to England. In 1626, he was able to persuade Orazio Gentileschi to settle in England, later to be joined by his daughter Artemisia and some of his sons. Rubens was an especial target, who eventually in 1630 came on a diplomatic mission, which included painting, and he later sent Charles more paintings from Antwerp. Rubens was very well-treated during his nine-month visit, during which he was knighted. Charles's court portraitist, Daniel Mytens, was a somewhat pedestrian Dutchman. Charles was very short, less than 5 feet (1.5 m) tall, and presented challenges to a portrait Artist.

A Sketch for one wall remains, but by 1638 Charles was too short of money to proceed. This was a Problem Velázquez did not have, but equally van Dyck's daily life was not encumbered by trivial court duties as Velázquez's was. In his visits to Paris in his last years van Dyck tried to obtain the commission to paint the Grande Gallerie of the Louvre without success.

Van Dyck's portraits certainly flattered more than Velázquez's; when Sophia, later Electoress of Hanover, first met Queen Henrietta Maria, in exile in Holland in 1641, she wrote: "Van Dyck's handsome portraits had given me so fine an idea of the beauty of all English ladies, that I was surprised to find that the Queen, who looked so fine in painting, was a small woman raised up on her chair, with long skinny arms and teeth like defence works projecting from her mouth..."

The series was a great success, but was his only venture into printmaking; portraiture probably paid better, and he was constantly in demand. At his death there were eighty plates by others, of which fifty-two were of artists, as well as his own eighteen. The plates were bought by a publisher; with the plates reworked periodically as they wore out they continued to be printed for centuries, and the series added to, so that it reached over two hundred portraits by the late 18th century. In 1851, the plates were bought by the Calcographie du Louvre.

Tate Britain held the exhibition Van Dyck & Britain in 2009. In 2016 the Frick Collection in New York had an exhibition "Van Dyck: The Anatomy of Portraiture", the first major survey of the artist's work in the United States in over two decades.

Some critics have blamed van Dyck for diverting a nascent, tougher English portrait tradition—of Painters such as william Dobson, Robert Walker and Isaac Fuller—into what certainly became elegant blandness in the hands of many of van Dyck's successors, like Lely or Kneller. The conventional view has always been more favourable: "When Van Dyck came hither he brought Face-Painting to us; ever since which time ... England has excel'd all the World in that great Branch of the Art’ (Jonathan Richardson: An Essay on the Theory of Painting, 1715, 41). Thomas Gainsborough is reported to have said on his deathbed "We are all going to heaven, and Van Dyck is of the Company."

A variety of factors meant that in the 17th century demand for portraits was stronger than for other types of work. Van Dyck tried to persuade Charles to commission him to do a large-scale series of works on the history of the Order of the Garter for the Banqueting House, Whitehall, for which Rubens had earlier done the huge ceiling paintings (sending them from Antwerp).

In England he developed a version of his style which combined a relaxed elegance and ease with an understated authority in his subjects which was to dominate English portrait-painting to the end of the 18th century. Many of these portraits have a lush landscape background. His portraits of Charles on horseback updated the grandeur of Titian's Emperor Charles V, but even more effective and original is his portrait of Charles dismounted in the Louvre: "Charles is given a totally natural look of instinctive sovereignty, in a deliberately informal setting where he strolls so negligently that he seems at first glance nature's gentleman rather than England's King". Although his portraits have created the classic idea of "Cavalier" style and dress, in fact a majority of his most important patrons in the nobility, such as Lord Wharton and the Earls of Bedford, Northumberland and Pembroke, took the Parliamentarian side in the English Civil War that broke out soon after his death.

The Iconography was highly influential as a commercial model for reproductive printmaking; now forgotten series of portrait prints were enormously popular until the advent of photography: "the importance of this series was enormous, and it provided a repertory of images that were plundered by portrait Painters throughout Europe over the next couple of centuries". Van Dyck's brilliant etching style, which depended on open lines and dots, was in marked contrast to that of the other great portraitist in prints of the period, Rembrandt, and had little influence until the 19th century, when it had a great influence on artists such as Whistler in the last major phase of portrait etching. Hyatt Mayor wrote: