At present, the problems of sustainable economic development still remain relevant for many regions. This research presents the idea that the stability of the territorial economy and the socially safe state of society are interrelated. The hypothesis was formulated that social immunity of the region is one of the sources of its sustainable economic development. To prove this hypothesis the following tasks were solved: social immunity assessment methodology was developed; the methodology was tested on the territories of the Ural region; the dependence of the territorial sustainable development on its social immunity was revealed. The methodology allows us to model the core of social immunity of any territory. It is based on the Frobenius norm, which reflects both positive and negative transformations of society. Approbation of the methodology for assessing social immunity was carried out on the example of the Sverdlovsk, Kurgan, Chelyabinsk and Tyumen oblasts during 2010-2018. The research made it possible to prove the hypothesis and to conclude that lack of social immunity in the region leads to poor economic effects received by business entities and the territory’s susceptibility to economic destabilizing external impacts, which are both random and systematic.