Securing critical networked cyber-physical systems (NCPSs) such as the power grid or transportation systems has emerged as a major national and global priority. The networked nature of such systems renders them vulnerable to a range of attacks both in cyber and physical domains as corroborated by recent threats such as the Stuxnet worm. Developing security mechanisms for such NCPSs significantly differs from traditional networked systems due to interdependence between cyber and physical subsystems (with attacks originating from either subsystem), possible cooperation between attackers or defenders, and the presence of human decision makers in the loop. The main goal of this research is to develop the necessary science and engineering tools for designing NCPS security solutions that are applicable to a broad range of application domains. This project will develop a multidisciplinary framework that weaves together principles from cybersecurity, control theory, networking and criminology. The framework will include novel security mechanisms for NCPSs founded on solid control-theoretic and related notions, analytical tools that allow incorporation of bounded human rationality in NCPS security, and experiments with real-world attack scenarios. A newly built cross-institutional NCPS simulator will be used to evaluate the proposed mechanisms in realistic environments. This research transcends specific cyber-physical systems domains and provides the necessary tools to building secure and trustworthy NCPSs. The broader impacts include a new infrastructure for NCPS research and education, training of students, new courses, and outreach events focused on under-represented student groups.