The United States has been the leader in fundamental research for the last seven decades. Fundamental research is overwhelming undertaken in or in conjunction with research-intensive universities, and since the 1950s they have depended on US Federal funding to make this possible. This support has been consistently championed by Congress, is popular across the political spectrum and enjoys long public backing, in no small part because there remains a widespread trust in the societal benefits it provides. Yet the US now faces a dilemma over the future of this national achievement and the supporting arrangements making it sustainable. The ‘social contract’ for science and research now looks more tentative than at any time since the Space Race. This paper examines why many US university leaders, faculty, experts and policy-makers are increasingly concerned, what is driving this and how they are responding. Building on 37 interviews with university, academic and government leaders, this study uses a mixed methodology to explore perceived institutional challenges and the politics around them, alongside the responses and strategies of US research-intensive universities in the context of global, national and regional policies. This paper examines tensions in the relationship between universities and government, and between researcher and public, combining perspectives from a sample of leading research universities and from national policy leaders to offer insight into the intersection of Federal policy and local operationalization. It concludes that for the future of US basic science and research two factors are likely to be decisive, being whether the strength of the public backing for funding university-based fundamental research continues, and how universities respond if, and in the assessment of many, when this support erodes. If the current research system is to remain viable, universities will need to make greater efforts to rebuild trust and understanding with the US public and litigate anew their raison d'etre at the center of US research.