Canvas paintings are layered structures composed of canvas support sized with animal glue, a preparatory layer of the ground, and paint and varnish layers on the top. Preventing or limiting humidity-induced stresses in these structures requires an understanding of the relevant processes and risks. A three-dimensional model of a canvas painting was used to analyse stresses and crack development in the two-layer structure comprised of a glue-sized canvas on a wooden stretcher with a layer of stiff chalk-glue ground representing a pictorial layer in historic canvas paintings. The model was subjected to a large relative humidity fall which induced shrinkage of the glue-sized canvas. The modelling revealed that when a stretcher with flexible wooden bars is considered, high tensile stresses arise in the ground layer at the corners of the painting, and cracks are formed in these areas in the direction perpendicular to the painting’s diagonal. Ratios of critical distances between cracks to the ground layer thickness for which stresses in the midpoints between the cracks dropped to below the level inducing fracture in the material were estimated for various magnitudes of the relative humidity drop and thicknesses of the ground layer. Increasing ground layer thickness limits the hygric response of the sized canvas and makes the paintings less vulnerable to humidity variations. The ratio of stress along the diagonal calculated for painting with one crack to the solution without cracks was described by the double Lorentz function. A simple procedure of calculating stress variations along the diagonal—using the function—on a sequential addition of cracks was developed. Cracks in central parts of canvas painting were found to be induced by permanent cumulative drying shrinkage of the oil-based paints and grounds due to the evolution of the molecular composition of the oil binder. The outcome of the modelling indicated that the risk of cracking of the pictorial layers in canvas paintings due to drops in ambient relative humidity was small.