This dissertation interrogates the relationships between humans and animals responsible for creating ‘pests’ as an element in the physical and intellectual landscape of rural South Africa in the 1910s through the 1930s. Through analysing four groups of animals deemed to be pests – herds of ‘rogue’ elephants; trypanosomes and big game; ‘wild birds’ and crop-devouring insects; veld rodents and Yersinia pestis – I show how the concept of pest and the organisms bearing this label fundamentally shaped settler agrarian societies. To do this, I synthesise three frames of analysis: pests, knowledge, and boundaries. Firstly, I examine how beings were constructed as ‘pest’ or ‘vermin’, how these organisms changed human/animal relations, and how settler and pest world-making was negotiated. Secondly, mobilising the category “settler science”, I explore how the agency of pests stimulated humans to produce, debate, and circulate knowledge about indigenous faunas with a view to controlling their movements, appetites, and settlement patterns. Thirdly, I chart how pests and those who studied them dismantled or reinforced boundaries between spheres of veld, farm, and town, as well as colonial modernist binaries of wild/domestic, useful/harmful, healthy/unhealthy fauna. By synthesising these frames, this dissertation integrates human, animal, and pathogenic agency into a single historical framework. Pestilent fauna have almost never been foregrounded as agents in South African history. Historians have largely regarded them as obstacles to settler expansion, victims of colonial violence, or treated them as metaphors that mediate human relationships. Bringing these beings to the forefront of my analysis allows me to rethink some key arguments in southern African histories of human-animal interaction. This dissertation shows that despite the efforts of settler colonists, spheres of nature and culture or human and animal were never thoroughly separated. The settlement and development of rural land depended not only on declarations of war on ‘vermin’, but alliances, negotiations, and concessions. Management of animals in the countryside engaged settlers in distinguishing their ‘natural allies’ from ‘natural enemies’ and subsequently attempting to conserve ‘useful’ or control ‘harmful’ fauna. A diverse array of actors, some entirely invisible in press and periodicals, contributed to this process: African and settler farmers, hunters, bureaucrats, game conservators, rodent-inspectors, and even pest-devouring carnivora. This thesis demonstrates that an expansive view of history of science, which foregrounds such experts in the production of knowledge without losing sight of the uneven power dynamics of colonialism is necessary to understand their contributions. Ultimately, between the 1910s and 1930s, policies of wildlife-management evolved in tandem with racial segregation. The management of both animals and humans stemmed from shared political imperatives justified by scientific racism: preservationism and white economic protectionism. Their ramifications continue to impact South Africa to this day.