A comparison of archaeological data in the Atacama Desert and Australian arid zone shows the impact of the El Niño-Southern Oscillation (ENSO) over the last 5,000 years. Using a dataset of > 1400 radiocarbon dates from archaeological sites across the two regions as a proxy for population change, we develop radiocarbon density plots, which are then used to explore the responses of these prehistoric populations to ENSO climatic variability. Under an ENSO regime, precipitation is in anti-phase between Australia and coastal Chile. As ENSO also impacts marine resource productivity in Chile and advection of moisture from the Amazon Basin, the net effects of ENSO on subsistence economies on either side of the Tropical Pacific should be positively correlated. This is confirmed by cross-spectral analysis of the radiocarbon density plots, which shows that population responses on either side of the Tropical Pacific are synchronous (r = > 0.82). Both the Australian and Atacama desert records show a general increase in population from about 13 cal kyr BP, increasing through the mid-Holocene climatic optimum. Following the intensification of ENSO around 3.7 cal kyr BP, we can correlate 'boom and bust' cycles of occupation on both sides of the Pacific, including the collapse of the Atacama desert coastal economy and cultural system at 3 cal kyr BP and the decline of both the Atacama highlands and Central Australian dryland populations between 3-2 cal kyr BP. After 2 cal kyr BP adaptive responses to ENSO varied between these regions, though all dryland populations show resurgence in occupation.