The Biden administration has made science and technology (S&T) a centerpiece of its early policy agenda, which includes ambitious targets for federal investments in research and development (R&D). In parallel, growing concerns among some members in Congress about U.S. global leadership in S&T-focused industries, especially in relation to China, have inspired a number of recent legislative efforts to strengthen the national innovation ecosystem. While President Biden’s first budget proposal works to build on this momentum in an effort to authorize historic increases to federal R&D agencies, challenges remain to ensure long-term, international competitiveness across scientific disciplines and advanced technologies. In this paper, we describe the U.S. federal budget process for R&D, discuss trends in federal R&D funding, and provide an outlook for the future of federal R&D expenditures during the Biden administration.