Saenredam was the son of the Northern Mannerist printmaker and draughtsman Jan Pietersz Saenredam (1565 - 1607), a follower of Goltzius whose sensuous naked goddesses are in great contrast with the work of his son. Pieter was born in Zaandam or, in those days, Saenredam. In 1612 he moved to Haarlem, where he became a pupil of Frans de Grebber and lived for the rest of his life. In 1614 he became a member of the Haarlem Guild of St. Luke.

A contemporary of the painter-architects Jacob van Campen, Salomon de Bray, and Pieter Post, he is noted for his surprisingly modern paintings of church interiors, the great bulk of his production. Saenredam achieved this modern look by using very even light, subtlely modulated, and removing detailed depiction of textures in his meticulously measured and drawn sketches of the churches he wanted to paint. He would make these sketches in pencil, pen, and chalk, and then add in watercolor to help give the sketch texture and color. The sketches are detailed, conveying the interior atmosphere through the clever use of light and graduated shadows. Saenredam often deliberately left people and church furniture out of his work, thus also focusing more attention on buildings and their architectural forms. Only after having made precise measurements, and precise sketches and drawings of the churches, he would take them to his studio where he started to create his paintings, often after a delay of many years. His emphasis on even light and geometry is brought out by comparing his works with those of the rather younger Emanuel de Witte, who left in the people, contrasts of light and such clutter of church furniture as remained in Calvinist churches, all usually ignored by Saenredam. Unlike de Witte's, Saenredam's views are usually roughly aligned with a main axis of the church.

Saenredam's paintings show medieval churches, usually Gothic, but sometimes late Romanesque, which had been stripped bare of their original decorations after the iconoclasm of the Protestant Reformation. Although Utrecht was the largest centre of the remaining Catholic population of the mainly Calvinist United Provinces, all the old churches were retained by the Protestants. The drawing for Saenredam’s Interior of St. Martin's Cathedral, Utrecht is typical. As a Catholic church the Cathedral had been highly decorated. Then, in the Dutch Revolt the church fell into Protestant hands, it was ‘cleaned’ of Catholic influences. The altarpieces and statuary were removed, and the walls and ceiling were white washed.

Alternatively, the paintings of church interiors by Saenredam and other 17th century Dutch painters have been interpreted as having less to do with religion and more with the new-found interest in perspective and with the Dutch interpretation (known as Dutch Classicism) of Palladio’s theories of proportion, balance and symmetry.

In any case, Saenredam wanted to memorialize his country during this time of change by documenting many of the country’s buildings. Many artists before him had specialized in imaginary and fanciful architecture, but Saenredam was one of the first to focus on existing buildings. According to the J. Paul Getty Trust “Saenredam’s church paintings… owe their poetry to his remarkable blend of fact and fiction. He began by making site drawings of buildings that record measurements and detail with archaeological thoroughness.” This meticulous preparation helped him to create such accurate and enchanting paintings. The measurements aided him in using scientific linear perspective, just like Andrea Pozzo. He was able to use his measurements to create a realistic image with depth.

The Utrecht Archives houses a large number of Saenredam's drawings. In the season 2000 - 2001 the Centraal Museum at Utrecht held a major exhibition of his drawings and paintings. Perhaps his best known works are a matching pair of oil paintings both titled Interior of the Buurkerk, Utrecht. One hangs in London's National Gallery, the other in the Kimbell Art Museum in Fort Worth, Texas. In their simplicity and semi-abstract formalism, they foreshadow more modern works such as those of Mondrian and Feininger.