Australia’s approach to its biosecurity and borders has always been two-pronged – quarantine first, vaccination second. This article asks what this combination looked like in practice by exploring two neglected smallpox vaccination campaigns directed towards Indigenous peoples in the early twentieth century. We argue these were important campaigns because they were the first two pre-emptive, rather than reactionary, vaccination programs directed towards First Nations people. Second, both episodes occurred in Australia’s northern coastline, where the porous maritime geography and proximity to Southeast Asia posed a point of vulnerability for Australian health officials. While smallpox was never endemic, (though epidemic), in Australia, it was endemic at various times and places across Southeast Asia. This shifting spectre of smallpox along the northern coastline was made even more acute for state and federal health officials because of the existing polyethnic relationships, communities, and economies. By vaccinating Indigenous peoples in this smallpox geography, they were envisioned and embedded into a ‘hygienic’ border for the protection of white Australia, entwining the two-prongs as one approach. In this article, we place public health into a recent scholarship that has ‘turned the map upside down’ to re-spatialise Australia’s history and geography to the north and its global connections, while demonstrating how particular coastlines and their connections were drawn into a national imaginary through a health lens.