Zernike, who was the son of mathematics teachers at Amsterdam in the Netherlands, studied at the university there, obtaining a doctorate in 1915. In 1913 he became assistant to the astronomer Jacobus Kapteyn at the University of Groningen, where he remained until his retirement in 1958, becoming professor of theoretical physics in 1920 and later of mathematical physics and theoretical mechanics.

Zernike's interest centered around optics and, more particularly, diffraction and in 1935 he developed the phase-contrast microscope. This uses the fact that light passing through bodies with a different refractive index from the surrounding medium has a different phase. The microscope contains a plate in the focal plane, which causes interference patterns and thus increases the contrast. For instance, it can make living cells observable without killing them by staining and fixing. The method of phase contrast also allows the detail in transparent objects or on metal surfaces to be observed.