The aim of this article is to explicate the assumptions of the new U.S. National Security Strategy and to provide a forecast of its potential implications for NATO’s eastern flank security environment. The main research problem is formulated as the following question: what is the significance of the new U.S. National Security Strategy for the security of NATO’s eastern flank? In order to address the primary research problem, it was analytically disaggregated into two subsidiary research questions. The first one is formulated as follows: what constitutes the essence of the new U.S. National Security Strategy? The second addresses the following issue: what potential impact might the new U.S. National Security Strategy have on the future security dynamics in Central and Eastern Europe? The following main hypothesis has been adopted: it is assumed that the current United States National Security Strategy, representing a radical departure from Washington’s long-standing foreign policy line pursued over recent decades, will significantly affect the dynamics of processes occurring within the security environment of NATO’s eastern flank. Furthermore, it is assessed that the implementation of the strategic assumptions by the United States may intensify the engagement of CEE states in the development of autonomous (national) and regional defence capabilities, as well as in the broad integration of the region, with a view to enhancing interoperability and military capabilities in the areas of deterrence and defence. The findings of the research indicate that the assumptions of the new U.S. National Security Strategy constitute an outgrowth of the long-term implementation of the political concept of „America First”, leading to a relative narrowing of the scope of U.S. national interests and a limitation of external resource engagement beyond designated priority areas. It may therefore be concluded that the assumptions of the U.S. National Security Strategy are likely to exert a substantial influence on the redefinition of the strategic objectives of NATO’s eastern flank states. These states may increasingly seek to autonomously develop and expand operational capabilities that have hitherto been provided by the United States, to intensify bilateral and regional security cooperation, and to pursue the institutionalisation of U.S. investments and defence commitments within the Central European security environment. The research methodology applied in this study comprises critical analysis and evaluation of the literature, systems analysis, reasoning, synthesis and prognostic method.