Bredius travelled widely, visiting various art collections in his youth, and worked at the Dutch Museum for History and Art before becoming director, from 1889 to 1909, of the Mauritshuis. He became a Rembrandt expert who had many differences of opinion with Cornelis Hofstede de Groot. He was a regular contributor to the historical magazines Oud Holland and Künstler-Inventare.
In 1922, he left the Netherlands for health reasons and settled in Monaco, publishing books in 1927 on Jan Steen and, in 1935, a catalog of Rembrandt paintings, often referred to in the literature as "Bredius 1935". He bequeathed his papers to the Rijksbureau voor Kunsthistorische Documentatie, and his art collection lives on in the Museum Bredius. He also bequeathed several Rembrandt paintings to the National Dutch collection, including Rembrandt's Homer Dictating his Verses.