At the end of the nineteenth century, three major port cities in the British Empire struggled with three different epidemic diseases. In Melbourne, Australia, a doctor named William Thomson uncovered a startlingly high mortality from tuberculosis; in Bombay, the plague began to take hold, resulting in the death of more than 500,000 of the city's residents; and in Belfast, typhoid fever rates attacked rich and poor alike, elevating mortality rates from the disease in the city beyond any other in the Empire, or indeed the western world. While historians have noted the existence of some of these epidemics, we have yet to understand precisely why these particular cities suffered so severely from these distinct diseases. This project draws on these three case studies—Melbourne, Bombay, and Belfast—to explore the relationship between empire-building, environmental management, and epidemic disease. It argues that the expansion of the late-nineteenth century British Empire was characterized by densely populated urban centers, massive reclamation and improvement projects, and deeply stratified systems of inequality, which together formed a unique system of environmental engineering. When applied to the ecosystems that sustained these major colonial cities, all of which represented unique climatic conditions and distinct colonial relationships, these alterations led to an increasingly competitive environment for particular microbes, resulting in the emergence and propagation of diseases unique to particular colonial ecologies. Responses to these epidemics, this project contends, altered the way British settlers interacted with imperial landscapes, and influenced knowledge concerning disease, environment, and urban spaces. In their attempt to engineer climates and ecosystems, the British destabilized them, and created a new series of challenges and changes to health, livelihood, and the imperial project as a whole.