Cornelis van Poelenburgh began his career as a pupil of Abraham Bloemaert. From 1617 to 1625 he worked in Italy. It is generally surmised that he worked in Florence for Cosimo II de Medici, the Grand Duke of Tuscany, between 1618 and 1621, returning to Utrecht in 1626. Otherwise he was in Rome, where he was exposed to the work of Adam Elsheimer, whose small luminous paintings on copper were to stay with Poelenburgh for many years. In 1627 he was commissioned by the States of Utrecht to paint a picture for the Princesse Amalia van Solm for which he was paid the princely sum of 575 florins. It is from this date that he gained a large studio of assistants and when his success begins to flourish.

In 1638 he travelled to London at the behest of Charles I and was supported by the sovereign during his stay. He enjoyed considerable aristocratic patronage for his small classical landscapes, usually on copper, although records show only five of his paintings ever entered the royal collection. He returned to Utrecht in 1641. He is also known to have added the staffage to paintings executed by other painters, including Jan Both, Willem de Heusch, Herman Saftleven and especially Hendrick van Steenwyck.

Poelenburgh was first elected to the Utrecht Guild in 1646. He is generally acknowledged as one of the most important first-generation Dutch Italianate (or 'schildersbent') painters. His early works show the influence of Bartolomeus Breenbergh as they worked closely together in Rome, and this is often the cause of confusion over their attribution. Poelenburgh, however, seemed more adept at the depiction of Italian light. Such was his following that he was patronised by some of the most important figures of the time. As well as the Grand Duke he painted pictures for Prince Frederick Henry of Orange Nassau, Charles I, the Baron von Wyttenhorst and the King of Bohemia. His enamel smooth landscapes generated a large following and he continued to influence painters long into the 18th Century.

Museums where examples of the artist's work can be found include:

Aix, Amiens, Copenhagen, Dresden, Florence (Pitti and Uffizi), Frankfurt, Geneva, Helsinki, Los Angeles (Getty), Madrid (Prado), Maryland (Walters), Milan, Ottawa, Stockholm, St. Petersburg, Toulouse and Venice.