Traditional infrastructure design approaches were born with industrialization. During this time the relatively stable environments allowed infrastructure systems to reliably provide service with networks designed to precise parameters and organizations fixated on maximizing efficiency. Now, infrastructure systems face the challenge of operating in the Anthropocene, an era of complexity. The environments in which infrastructure systems operate are changing more rapidly than the technologies and governance systems of infrastructure. Infrastructure systems will need to be resilient to navigate stability and instability and avoid obsolescence. This dissertation addresses how infrastructure systems could be designed for the Anthropocene, assessing technologies able to operate with uncertainty, rethinking the principles of technology design, and restructuring infrastructure governance. Resilience, in engineering, has often been defined as resistance to known disturbances with a focus on infrastructure assets. Resilience, more broadly reviewed, includes resistance, adaptation, and transformation across physical and governance domains. This dissertation constructs a foundation for resilient infrastructure through an assessment of resilience paradigms in engineering, complexity and deep uncertainty (Chapter 2), ecology (Chapter 3), and organizational change and leadership (Chapter 4). The second chapter reconciles frameworks of complexity and deep uncertainty to help infrastructure managers navigate the instability infrastructure systems face, with a focus on climate change. The third chapter identifies competencies of resilience in infrastructure theory and practice and compares those competencies with ‘Life’s Principles’ in ecology, presenting opportunities for growth and innovation in infrastructure resilience and highlighting the need for satisficed (to satisfy and suffice) solutions. The fourth chapter navigates pressures of exploitation and exploration that infrastructure institutions face during periods of stability and instability, proposing leadership capabilities to enhance institutional resilience. Finally, the dissertation is concluded with a chapter synthesizing the previous chapters, providing guidance for alternative design approaches for advancing resilient infrastructure. Combined, the work challenges the basic mental models used by engineers when approaching infrastructure design and recommends new ways of doing and thinking for the accelerating and increasingly uncertain conditions of the future.