For advanced imaging systems, e.g., projection systems for optical lithography, spatially varying aberration calibration is of utmost importance to achieve uniform imaging performance over the entire field-of-view (FOV). Here we present an efficient, accurate, and robust spatially varying aberration calibration method using a pair of 2-dimensional periodic pinhole array masks: the first mask in the object plane and the second mask in the image plane. Our method divides the entire FOV of the imaging system into partially overlapping subregions by using a measurement system consisting of an additional imaging system and a camera sensor. Each subregion, which covers several mask periods, is imaged onto a distinct camera pixel by the measurement system. Our method measures “Airy disc”-like patterns simultaneously in all subregions by scanning the second mask relative to the first mask over one mask p eriod. The number of subregions is equal to the number of camera pixels, and the sampling number of the measured patterns is equal to the scanning step number. The aberrations can be retrieved from the patterns measured in through-focus planes using an iterative optimization algorithm. In this paper, we performed experimental validation on a realistic lithography machine and demonstrate that our method is capable of retrieving the coefficients of 37 aberration terms, expressed as Zernike polynomials, with a sensitivity at nanometer scale.