Netscher's early years are shrouded in obscurity. He may have been born in Heidelberg. According to Arnold Houbraken's 17th century biographical study of Dutch painters, his father died when he was two years of age, and his mother, fleeing from the dangers of a civil war, carried him to Arnhem. Elsewhere it was suggested that he was from Prague, while current thoughts are that he may have been the son of a Rotterdam painter. In Arnhem he was adopted by a physician named A. Tullekens. At first he was destined for the profession of his patron, but owing to his great aptitude for painting he was placed under a local artist named Hendrick Coster, and in 1654 became a student of Ter Borch in Deventer, who had family connections to Tullekens. He was Ter Borch's most gifted pupil, probably worked as an assistant as well and he appears several times as a model on Ter Borch's paintings.
In 1658 he set out for Italy to complete his education there. However, he didn't get farther south than Bordeaux that fall, where he married Margaretha Godijn, a local woman, in 1659. There he toiled hard to earn a livelihood by painting those small cabinet pictures which are now so highly valued on account of their exquisite finish. After moving to The Hague in 1662, possibly because of the prosecutions of Protestants, he turned his attention to portrait-painting, and in this branch of his art was more successful. It is likely that he knew the painters Frans van Mieris, Sr. (1635?-1681) and Gerard Dou, but it is certain that he knew the painter Gerrit de Hooch from The Hague as his wife gave her name to Gerrit's new born daughter Margarita in 1676, the event being witnessed by Caspar as well as his wife. He was patronized by William III, and his earnings soon enabled him to gratify his own taste by depicting musical and conversational pieces.
It was in these that Netscher's genius was fully displayed. The choice of these subjects, and the habit of introducing female figures, dressed in glossy satins, were imitated from Ter Borch; they possess easy yet delicate pencilling, brilliant and correct colouring, and pleasing light and shade; but frequently their refinement passes into weakness. The painter was gaining both fame and wealth when be died prematurely in 1684, in The Hague. His sons Constantyn (1668-1722), and Theodorus (1661-1732), were also painters after their father's style, but inferior in merit.