Methods and systems for alignment of substrate-scale masks are described. The alignment methods presented may improve the uniformity and repeatability of processes which are impacted by the relative lateral position of a substrate-scale mask and a substrate. The methods involve measuring the “overhang” of the substrate at multiple locations around the periphery of the substrate-scale mask. Based on the measurements, the relative position of the substrate relative to the substrate-scale mask is modified by adjustment of the substrate and/or mask position. The adjustment of the relative position is made in one adjustment in embodiments. A feature of hardware and methods involves the capability of making measurements and adjustments while a substrate processing system is fully assembled and possibly under vacuum.