Herman Saftleven was the son of Herman Saftleven the Elder and the younger brother of Cornelis Saftleven. He moved from Rotterdam to Utrecht in 1632 marrying Anna van Vliet, the daughter of the architectural painter Hendrick, a year later. He remained in his adopted city for the rest of his life and had four children (two sons and two daughters). He became a citizen in 1659 and recorded a great number of views of the city over the years. His record of the city before and after the devastation caused by a storm in 1674 have proved invaluable for historical records.

Herman was primarily a landscape painter, although some of his early works depict peasant interiors in the manner of his brother Cornelis. They occasionally worked together, Herman painting the landscape and Cornelis the staffage. His first landscapes show the influence of Jan Van Goyen, and later Jan Both and Cornelis Poelenburgh, both Italianate artists from Utrecht. Later his landscapes were inspired by Roelandt Savery and by his own travels along the Moselle and in the Rhineland. These landscapes are often small in size and characterised by mountainous forests and rivers with peasants and villages, painted in dark green and brown tones. His attention to detail was meticulous and his style attracted many followers, including Jan Griffier and Christian George Schutz.

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

Amiens, Amsterdam, Berlin, Brussels, Budapest, Copenhagen, Dresden, Durham (Bowes), Edinburgh, Frankfurt, London (National Gallery), Los Angeles (Getty & LACMA), Munich, Rotterdam, San Francisco, Stockholm, St. Petersburg, Utrecht and Vienna (Kunsthistorisches).