In this conceptual paper, we argue that at times of crisis, what is sometimes called “evidence-based” or “science-driven” policymaking—establishing scientific truths and then implementing them—must be tempered by a more agile, deliberative and inclusive approach which acknowledges and embraces uncertainty. We offer pragmatism as one potential option, using examples from the UK to illustrate how such an approach might have changed particular crisis decisions and led to better outcomes. We propose that to better prepare for the next public health crisis, five pragmatism-informed shifts are needed in the science-policy relationship: from scientism to science-informed narrative rationality that emerges from practice; from knowledge-then-action to acting judiciously under uncertainty; from hierarchies of evidence to pluralist inquiry; from polarized camps to frame-reflective dialogue; and from an “inside-track” science-policy dialogue to greater participatory democracy. We suggest an agenda for a pragmatist-informed program of applied research on crisis public health policymaking.