High level of environmental safety of oil and gas regions is mainly achieved by solving the problems of economic effi ciency of natural resource use and of management of the complex of federal and regional projects for improving methods of environmental protection and environmental management. The purpose of the study is to develop a systematic rational approach to innovative development of environmental safety of the regions specializing in oil and gas on the basis of their interregional cluster organization in the conditions when it is essential to achieve higher levels of technological sovereignty and the dominance of circular economy strategies and decarbonization in the transforming global fuel and energy balance. To achieve the goal stated the author has carried out a theoretical study of the prospects of innovative resource directions for the development of the regional oil and gas industry and greening of regional economic systems as well as territorial distribution of regional industrial infrastructure to perform green energy transfer; theoretical studies of institutional mechanisms of strategic spatial development of Russia on the basis of interregional industrial cluster integration using highly profi table oil and gas revenues to develop and implement innovative principles of improving the environmental and economic effi ciency of the use of nature-like technologies, controlled environmental management, ESG factors, smart specialization of regions, local resource potential; regression analysis of dynamics and forecasting the volume of atmospheric pollution from stationary sources, the proportion of trapped and neutralized atmospheric pollutants from the total amount of gaseous pollutants emitted from stationary sources, as well as environment protection costs in the oil and gas regions; hierarchical clusterization of oil and gas regions by the amount of organizations applying innovations aimed at development of environmental safety, by material and energy fl ows, by reduction of CO2 emissions and use safe or less hazardous raw materials, by reduction of the level of environmental pollution and the use of waste recycling technologies.The research has been conducted on the example of the Volga Federal District where the oil and gas regions are represented by the subjects with the budget-forming petrochemical complex such as the Republic of Bashkortostan (RB), the Republic of Tatarstan (RT), the Udmurt Republic (UR), the Perm Territory (PT), the Orenburg Region (OR) and the Samara Region (SR). As a result of the study conducted the author developed the economic paradigm of environmental safety of oil and gas regions based on the application of principles of horizontal innovative and industrial, scientifi c, technological and fi nancial policy.