Hieronymus Bosch was born around 1450 as Jheronimus or Hieronymus (or, in Dutch, Jeroen) van Aken. The "van Aken" means "from Aachen", the German town from where his family originally came. Hieronymus is the Latin equivalent, and Jeroen the Dutch equivalent, of the name Jerome.

He was born, and lived all his life, in or near the flourishing merchant city of 's-Hertogenbosch (commonly known as "Den Bosch"), the capital of the Dutch province of Brabant, in the south of the present-day Netherlands. It is for this reason that he signed several of his paintings as Jheronimus Bosch, and he soon became widely known as Hieronymus Bosch.

Little is known of Bosch’s life or training. His father Anthonius van Aken, his grandfather Jan van Aken and several of his uncles were all painters, and it is generally assumed that either his father or one of his uncles taught the artist to paint.

At any rate, he apparently became a popular painter quite early in his lifetime and often received commissions from abroad. He became an independent master in 1486, and, in 1488, he joined the highly respected Brotherhood of Our Lady, an ultra-orthodox religious group based in 's-Hertogenbosch. The Brotherhood commissioned from him several altarpieces for the Cathedral of Saint John's, all of which are now lost.

Some time between 1479 and 1481, Bosch married Aleyt Goyaerts van den Meerveen, who was a few years older than the artist. The couple moved to the nearby town of Oirschot, where his wife had inherited a house and land, from her wealthy family.

Bosch’s death was recorded in the accounts of the Brotherhood of Our Lady in 1516, and he was buried on 9 August of that year. By the time of his death, he was internationally celebrated as an eccentric painter of religious visions who dealt in particular with the torments of hell, and his works featured in the private collections of noble families of the Netherlands, Austria and Spain. His style was imitated throughout the 16th Century and beyond, especially in the works of Pieter Bruegel the Elder.

Fewer than 25 paintings and a small number of drawings remain today that can be definitively attributed to Bosch. He never dated his paintings and the chronology of the paintings is difficult to determine with any precision.

Unusually for the time, he seems to have signed some of them. However, only seven of his paintings are signed, and there is some uncertainty whether all the paintings once ascribed to him were actually from his hand. The problem of attribution is exacerbated because his style was highly influential, and was widely imitated by his numerous followers.

In the late 16th Century, Philip II of Spain acquired many of Bosch's paintings, including some probably commissioned and collected by Spaniards active in Bosch's hometown. As a result, the Prado Museum in Madrid now owns several of his better-known paintings including The Garden of Earthly Delights, the circular tabletop of The Seven Deadly Sins and the Four Last Things, the The Haywain Triptych and The Extraction of the Stone of Madness.

Bosch's style was strikingly free and unique, and his vivid symbolism remains unparalleled to this day. In his fantastic and often terrifying visions, he expressed an intense pessimism, reflecting the anxieties of his time, which was one of social and political upheaval, as well as of religious zeal.

The city of ‘s-Hertogenbosch was religiously progressive, and Erasmus had been educated at one of the houses of the Brethren of the Common Life in the town, which has led many to suggest that Bosch’s art was inspired by heretical points of view (such as those of the Cathars or Adamites).

Another strain of interpretation dating back to the 16th Century assumes that his work was created merely to titillate and amuse, and some early art historians regarded him merely as "the inventor of monsters and chimeras" or "wondrous and strange fantasies ... often less pleasant than gruesome to look at".

More recent scholarship, however, has come to view Bosch’s vision as less fantastic and more a reflection of the orthodox religious belief systems of his age. His depictions of sinful humanity and his conceptions of Heaven and Hell are now seen as consistent with those of late medieval didactic literature and sermons. Bosch’s art was probably created to teach specific moral and spiritual truths, and often represents visual translations of verbal metaphors and puns drawn from both biblical and folkloric sources.

Some writers see Bosch as a prototype medieval surrealist, and parallels are often made with the 20th Century Spanish surreal artist, Salvador Dali. Other writers have attempted to interpret his imagery using the language of Freudian psychology and dream analysis.