The science instruments (SIs) comprising the James Webb Space Telescope (JWST) Integrated Science Instrument Module (ISIM) were tested in three cryogenic-vacuum test campaigns in the NASA Goddard Space Flight Center (GSFC)'s Space Environment Simulator (SES) test chamber.In this paper, we describe the results of optical wavefront-error performance characterization of the SIs. The wavefront error is determined using image-based wavefront sensing, and the primary data used by this process are focus sweeps, a series of images recorded by the instrument under test in its as-used configuration, in which the focal plane is systematically changed from one image to the next. High-precision determination of the wavefront error also requires several sources of secondary data, including 1) spectrum, apodization, and wavefront-error characterization of the optical ground-support equipment (OGSE) illumination module, called the OTE Simulator (OSIM), 2) f/# and pupil-distortion measurements made using a pseudo-nonredundant mask (PNRM), and 3) pupil geometry predictions as a function of SI and field point, which are complicated because of a tricontagon-shaped outer perimeter and small holes that appear in the exit pupil due to the way that different light sources are injected into the optical path by the OGSE. One set of wavefront-error tests, for the coronagraphic channel of the Near-Infrared Camera (NIRCam) Longwave instruments, was performed using data from transverse translation diversity sweeps instead of focus sweeps, in which a sub-aperture is translated and/or rotated across the exit pupil of the system.Several optical-performance requirements that were verified during this ISIM-level testing are levied on the uncertainties of various wavefront-error-related quantities rather than on the wavefront errors themselves. This paper also describes the methodology, based on Monte Carlo simulations of the wavefront-sensing analysis of focus-sweep data, used to establish the uncertainties of the wavefront-error maps.