Intergovernmental science organizations (IGSOs) address many challenges of the 21st century. Several countries of the Global South have joined established IGSOs or have created new ones. Yet we know little about their interests in IGSOs. Our study addresses this blind spot by investigating which objectives Southern actors pursue in IGSOs and under which conditions they are likely to achieve their objectives. Using insights from three strands of literature, we compare four IGSOs with Southern participation: the European Organization for Nuclear Research, the International Thermonuclear Experimental Reactor, the Square Kilometer Array, and the African Lightsource. We show that countries of the Global South pursue a multitude of political and scientific objectives in IGSOs, ranging from capacity-building to casting off political isolation. Moreover, we demonstrate that Southern countries have varying chances of attaining these objectives, depending on their scientific community, domestic politics, industrial capacities and in some cases geographic location as well as an IGSO’s maturity.