Brussels tapestry workshops produced tapestry from at least the 15th century, but the city's early production in the Late Gothic International style was eclipsed by the more prominent tapestry-weaving workshops based in Arras and Tournai. In 1477 Brussels, capital of the Duchy of Brabant, was inherited by the house of Habsburg; and in the same year Arras, the prominent center of tapestry-weaving in the Low Countries, was sacked and its tapestry manufacture never recovered, and Tournai and Brussels seem to have increased in importance.

The only millefleur tapestry to survive together with a record of its payment was a large heraldic millefleur carpet of very high quality made for Duke Charles the Bold of Burgundy in Brussels, of which part is now in the Bern Historical Museum. Sophie Schneebalg-Perelman's attribution to Brussels of The Lady and the Unicorn at the Musée de Cluny may well be correct.

The great period of Renaissance weaving in Brussels dates from the weaving entrusted by Pope Leo X to a consortium of its ateliers of the Acts of the Apostles after cartoons by Raphael, between 1515 and 1519. Leo must have been motivated by the already high technical quality of Brussels tapestries.

The conventions of a monumental pictorial representation with the effects of perspective that would be expected of a fresco or other wall decoration were applied for the first time in this prestigious set; the framing of the central subject within wide borders that proved able to be brought up to date in successive weavings, was also introduced in these 'Raphael' tapestries.

The prominent painter and tapestry designer Bernard van Orley (who trained in Italy) transmuted the Raphaelesque monumental figures to forge a new tapestry style that combined the Italian figural style and perspective rendition with the "multiple narratives and anecdotal and decorative detail of the Netherlandish tradition," according to Thomas P. Campbell.

A Hunts of Maximilian suite, depicting hunting in each of the months, was woven to cartoons by Bernard van Orley ca1531-33. A suite of nine allegorical Honors that celebrated the coronation of Charles V as king of Germany and his assumption of the title of Holy Roman Emperor-elect in 1520 survives among the Patrimonio Nacional, Palacio Real de la Granja de San Ildefonso, Spain. Van Orley's pupils, Pieter Coecke van Aelst and Michiel Coxie, also provided cartoons for Brussels looms under the general influence of Italian painting. A set of Seven Deadly Sins, of which four survive, are recognized as Pieter Coecke van Aelst's masterpieces.

Brussels quickly took pre-eminence in tapestry weaving. In 1528 a city decree ordained that each piece of Brussels tapestry over a certain size bear the woven mark of a red shield flanked by two B's; this aids in identifying Brussels production. Each tapestry was to include the woven mark of the maker or the merchant who commissioned the tapestry for resale. The public market for tapestry sales was Antwerp.

Though he was the arch-rival of the Habsburgs, Francis I of France commissioned tapestries from Brussels and Antwerp in the early years of his reign. After the arrival of Primaticcio at Fontainebleau in 1532, it was to Brussels that the Italian painter was sent, with a preparatory drawing of a Story of Scipio Africanus to be rendered as a cartoon, with which he returned.