Netscher set out for Italy and got no further than Bordeaux. He had letters of introduction, a plan to complete his artistic education in Rome, and a ship booked. In Bordeaux he fell in love with Margaretha Godyn, married her in 1659, and never continued the journey. The rest of his career happened in The Hague.

He was born around 1639, probably in Heidelberg or Prague. His father, a sculptor from Stuttgart, died when Caspar was two. During the siege of Heidelberg his mother fled with four children; two older brothers died of hunger. He was placed with the painter Hendrick Coster in Arnhem, then became a student of Gerard ter Borch in Deventer. Ter Borch was the most important influence on his work; Netscher appears as a model in several of Ter Borch's paintings.

His portraits and genre scenes of The Hague's fashionable society were painted with a precision that earned comparisons to Vermeer. He rendered fabrics, lace and reflected light with miniaturist exactitude. Cosimo III de' Medici bought his work. He kept drawings of finished paintings as records (ricordi), noting prices, patron names and colour choices.

He was plagued by gout but remained productive, sometimes painting from bed. Two of his sons, Constantyn and Theodorus, became painters in his style. A third, Anthonie, emigrated to Batavia. He died in The Hague in 1684, at about forty-five.