Axial chemical inhomogeneity in metals is a common issue in the production of thick-sheeted products from microalloyed pipe steels. To study the behavior of liquation zones during rolling, a model has been developed to describe and analyze the stress-strain state throughout the rolled section, including the axial chemical inhomogeneity zone. This mathematical model was implemented using the finite element software Abaqus. This paper investigates the influence of deformation direction (longitudinal and transverse), degree of deformation, and metal temperature on the changes in chemical inhomogeneity during thick-sheeted rolling. It has been found that the degree of deformation has the greatest influence on the transformation of chemical inhomogeneity. The results suggest that rolling with a reduction of at least 10–15% is optimal, since this level of deformation significantly enhances the fragmentation of chemical inhomogeneity. This is achieved by increasing the stress and strain intensities in the axial zone, which helps break the bonds between different areas of chemical inhomogeneity of the metal.