To realize the promise of quantum computing, we must move beyond the current era of Noisy Intermediate Scale Quantum (“NISQ”) machines and progress toward scalable fault-tolerance. Achieving fully fault-tolerant computing is difficult because of the complexity and large overheads imposed by conventional approaches to quantum error correction (QEC) that are being pursued by commercial entities. New ideas are needed to make QEC more practical, and to find the use cases that can benefit from detecting or partially correcting errors in the near term. The aim of this Quantum Leap Challenge Institute (U.S. National Science Foundation QLCI Award #2552449) is to advance the science and engineering of practical quantum error correction by creating a community where scientists and engineers from a wide range of disciplines can contribute to a holistic understanding of the hardware and software stack required to realize large-scale, error-corrected quantum hardware. This is a highly interdisciplinary effort that requires strong communication among experts working at different layers of the stack, ranging from hardware at the bottom to algorithms at the top. We will therefore organize ourselves into three overlapping research thrusts. The first will focus on quantum hardware, advancing our experimental capabilities in the field of error correction and supporting hardware such as quantum nondemolition measurement and real-time decoders. The second will focus on adapting algorithms and applications to take advantage of near-term hardware opportunities such as erasure qubit (in both superconducting and neutral atom systems) and ‘partial’ correction techniques such as post-selection and error mitigation. The third thrust will explore QEC theory from the computer science and physics points of view, building software tool chains with a focus both on long-term large-scale machines and on bridging between these future machines and near-term, small- and medium-scale QEC demonstrations. A fourth thrust will spur workforce development and educational efforts across the center and beyond.