Global health is becoming an important area of inquiry and learning in North American research universities, stemming from on-going and new commitments to the field by multiple governmental and non-governmental agents. External demands for research and education in global health require enhanced inter-disciplinary, inter-sectoral and international collaborations, all perceived as growing trends but often not easily accommodated in universities. This paper investigates how four leading universities in Canada and the US have entered the field of global health, exploring the relationships among national contexts, academic structures, and institutional strategies. Content analysis of institutional records is triangulated with data from sixty interviews with academic leaders and researchers at Harvard, Johns Hopkins, McGill and Toronto. Resource asymmetries emerge as an important differentiating factor shaping the emergence of global health in the American and Canadian institutions. Domestic sources of support and previous academic structures provided important cumulative advantages to the US campuses in claiming national and international leadership in the field.